Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
1999-07-15
2001-05-22
Jarvis, William R. A. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
C514S646000, C514S653000
Reexamination Certificate
active
06235793
ABSTRACT:
The present invention relates to a novel indication of &bgr;
3
-adrenergic receptor agonists.
More particularly, the invention relates to the use of &bgr;
3
-adrenergic receptor agonists for the preparation of wound healing drugs.
It is known that &bgr;
3
-adrenergic receptor agonists are capable of being used for the treatment of obesity and diabetes, although the clinical proof of this activity has not been provided with certainty.
It is also known that &bgr;
3
-adrenergic receptor agonists, hereafter abbreviated to “&bgr;
3
-agonists”, have been proposed as intestinal spasmolytics for the treatment of gastrointestinal diseases, more particularly inflammatory bowel disease (IBD) and irritable colon syndrome, and for protection of the gastrointestinal tract from the side effects of non-steroidal anti-inflammatory drugs.
The term “&bgr;
3
-agonists” includes &bgr; receptor agonist compounds which have been defined as “atypical” or “non-&bgr;
1
non-&bgr;
2
” and which are now recognized as a subtype of adrenergic receptor called “&bgr;
3
”.
The treatment of wounds which do not heal represents a serious clinical problem that is difficult to solve because the healing of wounds involves a complex series of phenomena which overlap and which are difficult to control globally.
Growth factors, especially basic Fibroblast Growth Factor (bFGF, Biol. Pharm. Bull., 1996, 19(4), 530-535) and acidic Fibroblast Growth Factor (aFGF, J. Invest. Dermatol., 1995, 104, 850-855), as well as sphingosylphosphorylcholine, J. Invest. Dermatol., 1996, 106, 232-237, have been proposed as wound healing agents.
It has now been found that &bgr;
3
-agonists possess a definite activity on the healing of wounds in mammals.
More particularly, it has been found that &bgr;
3
-agonists act by accelerating the healing of skin wounds in diabetic mammals.
Thus, according to one of its features, the present invention relates to the use of &bgr;
3
-agonists for the preparation of pharmaceutical compositions intended for accelerating the healing of wounds.
More particularly, the invention relates to the use of &bgr;
3
-agonists for the preparation of wound healing drugs.
&bgr;
3
-agonists which are useful according to the present invention are represented by formula (I):
in which:
X is hydrogen, a halogen, a trifluoromethyl group or a (C
1
-C
4
)alkyl group; and
R is hydrogen or a methyl group which is unsubstituted or substituted by a carboxyl or lower carbalkoxy group, and their pharmaceutically acceptable salts, indicated in EP 0 211 721 and EP 0 303 546, which describe compounds of formula (1) which are useful as intestinal spasmolytics.
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K. Kuratani et al., “Enhancement of Gastric Mucosal Blood Flow by &bgr;-3 Adrenergic Agonists Prevents Indomethacin-Induced Antral Ulcer in the Rat”,J. Pharmacol. Exp. Ther., 270 (2), 1994, pp. 559-565.
Y.-T. Shen et al., “Peripheral Vascular Effects of &bgr;-3 Adrenergic Receptor Stimulation in Conscious Dogs”,J. Pharmacol. Exp. Ther., 268 (1), 1994, pp. 466-473.
Derwent Abstract No. AN 95-332486 (JP 07228543A), 1995.
JRS Arch et al., “Prospects for &bgr;3-Adrenorecptor Agonists in the Treatment of Obesity and Diabetes”,Int. J. Obesity, 20 (3), 1996, pp. 191-199.
Arnone Michele
Bernat Andre
Herbert Jean-Marc
Alexander Michael D.
Dupont Paul E.
Jarvis William R. A.
Kim Vickie
Sanofi-Synthelabo
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