Therapeutic compound-fatty acid conjugates

Details Therapeutic compound-fatty acid conjugates Therapeutic compound-fatty acid conjugates

1998-01-30

2002-03-05

Carr, Deborah D. (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Fatty compounds having an acid moiety which contains the...

C554S104000, C554S227000

Reexamination Certificate

active

06353124

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to therapeutic conjugates which comprise a therapeutic compound bound to one to three acyl groups derived from fatty acids and to methods involving the use of these compounds. In particular the present invention relates to nonsteroidal anti-inflammatory compounds bound to one to three acyl derivatives of fatty acids.
BACKGROUND OF THE INVENTION
Among the most commonly used therapeutic agents are the nonsteroidal anti-inflammatory drugs. These are typically broken into three major groups:
carboxylic acids,
pyrazoles, and
oxicams.
Of particular interest in the present invention are the nonsteroidal anti-inflammatory agents which include a carboxylic acid group such as salicylates. Of these nonsteroidal anti-inflammatory drugs the most commonly used compounds are acetylsalicylic acid (aspirin), ibuprofen and indomethacin.
The present inventors have now discovered that the nonsteroidal anti-inflammatory drugs and other therapeutic compounds can be linked to one to three fatty acids. These new compounds are believed to improve the transdermal delivery, transdermal uptake, half-life and/or other modes of delivery of these nonsteroidal anti-inflammatory and other therapeutic agents. Further, it is believed that these novel compounds will aid in the oral, internasal and intraocular delivery of the nonsteroidal anti-inflammatory drugs and other therapeutic agents.
SUMMARY OF THE INVENTION
Accordingly, in a first aspect the present invention consists in a compound of the following formula:
in which X is a therapeutic compound
Y is absent or is one or two amino acids or a peptide or spacer group
B is H or CH
2
O—R
3
; and
R
1
, R
2
and R
3
are the same or different and are either hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid (saturated or unsaturated) with the proviso that at least one of R
1
, R
2
and R
3
is an acyl group derived from a fatty acid.
In a second aspect the present invention consists in a compound of the following formula:
X—Y—NH—CH
2
—CH
2
O—R
4
in which X represents a therapeutic compound,
Y is absent or is one or two amino acids or a peptide or spacer group, and R
4
is an acyl group derived from a fatty acid.
In a third aspect the present invention consists in a method of prolonging the activity of a nonsteroidal anti-inflammatory compound comprising administering the compound in the form
in which X is the nonsteroidal anti-inflammatory compound
Y is absent or is one or two amino acids or a peptide or spacer group
B is H or CH
2
O—R
3
; and
R
1
, R
2
and R
3
are the same or different and are either hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid with the proviso that at least one of R
1
, R
2
and R
3
is an acyl group derived from a fatty acid.
In a fourth aspect the present invention consists in a method of prolonging the activity of a nonsteroidal anti-inflammatory compound comprising administering the compound in the form:
X—Y—NH—CH
2
—CH
2
O—R
4
in which X represents the nonsteroidal anti-inflammatory compound
Y is absent or is one or two amino acids or a peptide or spacer group, and R
4
is an acyl group derived from a fatty acid.
In a fifth aspect the present invention consists in a method of treating burns comprising administering a compound of the formula:
in which X is ibuprofen
Y is absent or is one or two amino acids or a peptide or spacer group
B is H or CH
2
O—R
3
; and
R
1
, R
2
and R
3
are the same or different and are either hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid with the proviso that at least one of R
1
, R
2
and R
3
is an acyl group derived from a fatty acid.
In a sixth aspect the present invention consists in a method of treating burns comprising administering a compound of the formula:
X—Y—NH—CH
2
—CH
2
O—R
4
in which X is ibuprofen
Y is absent or is one or two amino acids or a peptide or spacer group, and R
4
is an acyl group derived from a fatty acid.
As will be recognised by persons skilled in the art, the compound of the first aspect of the present invention consists of a therapeutic compound linked, optionally via an amino acid(s) to a tromethamine derivative to which is linked an acyl group derived from a fatty acid(s). Similarly, the compound of the second aspect can be recognised as a therapeutic agent linked, optionally via an amino acid(s) to an ethanolamine derivative to which is linked an acyl group derived from a fatty acid.


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