Acylated phospholipid drugs

Details Acylated phospholipid drugs Acylated phospholipid drugs

1992-04-16

2003-08-05

Geist, Gary (Department: 1204)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Phosphorus containing other than solely as part of an...

C514S078000, C514S088000, C554S078000, C554S079000, C554S080000, C554S081000

Reexamination Certificate

active

06602861

ABSTRACT:

This invention relates to means for improving the efficacy of a drug containing a carboxy group by esterifying the drug to a glycerol phospholipid. The present invention also relates to the product obtained therefrom and the method of using the resulting product to treat various pathological conditions in animals, especially mammals.
SUMMARY OF THE INVENTION
The present invention relates to a method for improving the efficacy of a drug containing a carboxy group or a hydrolyzable group that can be converted to a carboxy group by acylating a glycerol phospholipid ester to the drug. The present invention also relates to the resulting product and the method of using the product to treat diseases in animals, especially mammals.
More specifically, the present invention relates to a new method for improving the efficacy of a drug containing a carboxy group or the hydrolyzable group referred to hereinabove or its pharmaceutically acceptable salt by esterifying the carboxy containing drug to the glycerol backbone of a glycerol phospholipid ester, the glycerol phospholipid ester having the formula:
or pharmaceutically acceptable salts thereof;
wherein one of R
1
and R
2
is hydrogen and the other is hydrogen, alkyl fatty acid acyl group having 4-26 carbon atoms or alkyl heteroatom fatty acid acyl group having 3-25 carbon atoms or
R
3
is hydrogen or lower alkyl and
R
4
is hydrogen; hydrocarbyl containing from 1 to 22 carbon atoms in a principal chain and up to a total of 26 carbon atoms, said principal chain may contain 1-5 double bonds or 1-2 triple bonds; phenyl which may be unsubstituted or substituted with lower alkyl; naphthyl, which may be unsubstituted or substituted with lower alkoxy; or R
5
ZR
6
;
Z is O or S;
R
5
and R
6
are independently a hydrocarbyl chain containing from 1-21 carbon atoms in the principal chain and up to a total of 25 carbon atoms, said chain may be completely saturated or may contain 1-5 double bonds or 1-2 triple bonds, such that the sum of carbon atoms in R
3
and R
4
is not greater than 25;
R is a naturally occurring polar group characteristic of a glycerophospholipid isolated from endogenous sources; preferred examples of
wherein R
8
and R
9
are independently hydrogen or lower alkyl, and preferably hydrogen.
The utility of the resulting phospholipid compounds from the above esterification reaction is similar to that of the drug prior to undergoing the reaction described hereinabove. Thus, the present invention is also directed to the acylated (esterified) phospholipid resulting from the acylation (esterification) reactions described hereinabove as well as the use of the acylated phospholipid for treating diseases in animals, especially mammals.


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