Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Utility Patent
1999-05-12
2001-01-02
Dentz, Bernard (Department: 1612)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
C514S443000, C514S469000, C514S569000, C514S621000, C514S622000, C514S657000, C514S681000, C514S682000, C514S719000, C514S729000
Utility Patent
active
06169111
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to the use of prostaglandins and prostaglandin analogues for the treatment of glaucoma and ocular hypertension. As used herein, the terms “prostaglandin” and “PG” shall refer to prostaglandins and derivatives and analogues thereof, except as otherwise indicated by context.
Naturally-occurring prostaglandins, especially prostaglandins of the F series (such as PGF
2&agr;
and the E series (such as PGE
2
), are known to lower intraocular pressure (IOP) after topical ocular instillation, but can cause conjunctival hyperemia and/or edema as well as inflammation. Many synthetic prostaglandins have been observed to lower intraocular pressure, but most such compounds also produce the aforementioned side effects which significantly limit their clinical utility.
Various attempts have been made to overcome these well-known side-effects. Some have synthesized derivatives of naturally-occurring prostaglandins in an attempt to design out selectively the side effects while maintaining the IOP-lowering effect. See, e.g., Stjernschantz et al. (U.S. Pat. Nos. 5,422,368 and 5,321,128), Woodward et al. (U.S. Pat. No. 5,093,329), Chan et al. (WO 92/08465 and U.S. Pat. No. 5,446,041). Others, including Ueno et al. (EP 330 511 A2) and Wheeler (EP 435 682 A2) have tried complexing prostaglandins with various cyclodextrins.
SUMMARY OF THE INVENTION
It has now been unexpectedly discovered that certain conformationally rigid analogues of PGF
2&agr;
will lower or control IOP with no or significantly reduced side effects of conjunctival hyperemia and/or edema. An agent which exhibits comparable efficacy, but with reduced side effects when compared to other agents, is said to have an improved therapeutic profile.
While bound by no theories, it is believed that increased conformational rigidity resulting from the presence of a bicyclic ring at the terminus of the omega chain of the prostaglandins of the present invention allows increased discrimination amongst the various PG receptors, which, in turn, allows a higher separation of desirable and undesirable activities, and therefore an improved therapeutic profile.
REFERENCES:
patent: 4004021 (1977-01-01), Bowler et al.
patent: 4152527 (1979-05-01), Hess et al.
patent: 4321275 (1982-03-01), Bowler et al.
patent: 5093329 (1992-03-01), Woodward
patent: 5151444 (1992-09-01), Ueno et al.
patent: 5302617 (1994-04-01), Ueno
patent: 5321128 (1994-06-01), Stjernschantz et al.
patent: 5422368 (1995-06-01), Stjernschantz et al.
patent: 5446041 (1995-08-01), Chan et al.
patent: 5741810 (1998-04-01), Burk
patent: 5834498 (1998-11-01), Burk
patent: 0330511 A2 (1989-08-01), None
patent: 0435682 A2 (1991-07-01), None
patent: 0561073 A1 (1993-09-01), None
patent: 0603800 A1 (1994-06-01), None
patent: 0667160 A2 (1995-08-01), None
patent: 1539268 (1979-01-01), None
patent: WO 92/02496 (1992-02-01), None
patent: WO 92/08465 (1992-05-01), None
patent: WO 94/06432 (1994-03-01), None
patent: WO 94/08587 (1994-04-01), None
patent: WO 96/10407 (1996-04-01), None
patent: WO 96/36599 (1996-11-01), None
Braun, et al.,Effect of ZK 110.841 on Cerebral Vascular Contraction and TXA2-Release Caused by Thrombin-Stimulated Platelets, Archives of Pharmacology 339 Suppl:R37, No. 148 (1989).
Hayashi et al.,Prostaglandin Analogues Possessing Antinidatory Effects. I. Modification of the &ohgr; Chain,J. Med. Chem. 23(5):519-524 (1980).
Ney, Potent Inhibition of FMLP-Induced Neutrophil Activation by the PGD2Analogue ZK 110.841,Archives of Pharmacology, 339 Suppl:R38, No. 150 (1989).
New Research Drug DLO/8149, Drug License Opportunities (IMSWORLD Publications) (Jun. 25, 1990).
Schaaf et al., Structure-Activity Studies of Configurationally Rigid Arylprostaglandins,J. Med. Chem.26(3):328-334 (1983).
Bishop John E.
Dean Thomas R.
Hellberg Mark R.
Zinke Paul W.
Alcon Laboratories Inc.
Copeland Barry L.
Dentz Bernard
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