Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-06-18
2003-01-14
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S445000, C514S448000, C514S468000, C514S469000, C514S538000, C514S562000
Reexamination Certificate
active
06506789
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a pharmaceutical composition for the prevention or treatment of itching comprising a prostaglandin D
2
(PGD
2
) receptor antagonist.
BACKGROUND ART
PGD
2
is a major prostanoid released from mast cells in which it is produced through PGG
2
and PGH
2
from arachidonic acid by the action of cyclooxygenase activated by immunological or unimmunological stimulation. PGD
2
has been known to cause allergic disorders such as allergic rhinitis and allergic conjunctivitis because it shows various physiological effects such as induction of nasal obstruction, vasodilator effect, wandering of eosinophils and the like. Accordingly, PGD
2
receptor antagonists have been thought to be useful for the treatment thereof (WO97/00853).
Moreover, a large quantity of PGD
2
is also released from macrophages, so PGD
2
may play a role in causing an inflammatory response independent of allergy.
On the other hand, itching has been known to be accompanied by diseases such as atopic dermatitis, urticaria, allergic rhinitis, allergic conjunctivitis and the like as well as inflammatory responses such as swelling and the like. Moreover, the action accompanied by itching, for example scratching, knocking and the like may worsen the condition of the above-mentioned diseases. Therefore, the development of a compound for the treatment of itching has been desired, which is further expected to be a pharmaceutical composition for the prevention or treatment of diseases secondarily caused by the action against itching, for example cararacta, retinal detachment, inflammation, infection, dysgryphia and the like.
At present, antihistaminic agents are used as therapeutic agents for itching. They show an effect on swelling, but the effect against itching is by no means sufficient. Thus, it is suggested in Allergology Int., 1997, 46, 117-124 that itching may be caused by a mediator other than histamine.
A PGD
2
receptor antagonist used in the present invention has been known to be useful for the treatment of allergic condition caused by PGD
2
such as rhinitis and the like (WO97/00853). Any positive data concerning the prevention or treatment of itching has not been described.
On the other hand, it is described in J. Pharmacol. Exp. Ther., 279, 137-142, 1996 that instillation of PGD
2
in guinea pig induces itching, which is inhibited by a PGD
2
receptor antagonist, BWA868C. But it is not described that a PGD
2
receptor antagonist is useful for the treatment of itching caused by allergy. Further described is that a PGD
2
receptor antagonist, BWA868C, can not inhibit itching caused by antigens at all, which is similar to disease models.
On the other hand, it is described that Ramatroban, inhibiting the contraction of smooth muscle of bronchus caused by TXA
2
or PGD
2
stimulation, is efficacious against contact dermatitis or atopic dermatitis mediated by delayed allergy (WO97/44031). However, Ramatroban described in said specification is a TXA
2
receptor antagonist, but not a PGD
2
receptor antagonist. Moreover, the therapeutic effect of Ramatroban against atopic dermatitis is based on the suppression of swelling caused by the delayed-type allergy reaction. Thus, the suppression effect against itching is not described. Therefore, it is not suggested that a PGD
2
receptor antagonist of the present invention suppresses itching and useful for the treatment of atopic dermatitis.
DISCLOSURE OF INVENTION
PGD
2
, a mediator mass-produced through allergy reaction, is supposed to play an important role as a mediator in itching. Indeed, we have discovered through an experiment using mice that a PGD
2
receptor antagonist is efficacious against itching to accomplish the present invention. Therefore, the present invention provides a composition for the prevention or treatment of itching comprising a PGD
2
receptor antagonist. In detail, the present invention provides a composition for the prevention or treatment of itching caused by an antigen, especially a composition for the treatment of itching derived from atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis or contact dermatitis.
A PGD
2
receptor antagonist used in the present invention has an activity of preventing or treating itching and so it is able to be used for a pharmaceutical composition for the prevention or treatment of itching. The term “itching” to be used in the present specification means itching caused by an allergic reaction or a non-allergic reaction.
The allergic reaction means reactions caused by the activation of mast cell, basophil and the like due to the reaction of an antigen with the antigen-specific IgE and the delayed-type allergy reaction such as contact dermatitis. The non-allergic reaction means a reaction which is independent of IgE and caused by mast cells, basophils and the like activated by a chemical substance or the like.
The PGD
2
receptor antagonist suppresses itching derived from the allergic reaction or non-allergic reaction and is useful for the prevention or treatment of the accompanying inflammation such as atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis, contact dermatitis and the like.
Moreover, the PGD
2
receptor antagonist is useful for the prevention or treatment of a secondary disease such as cararacta, retinal separation, inflammation, infection, dysgryphia or the like, which is caused by an action accompanied by itching, for example, scratching, knocking and the like.
BEST MODE FOR CARRYING OUT THE INVENTION
The PGD
2
receptor antagonist used in the present invention has an activity of preventing or treating itching. Among them, preferred is a composition for the prevention or treatment of itching comprising a compound of the following formula (I).
In a preferred embodiment, the PGD
2
receptor antagonist includes a compound of the formula (I):
R is hydrogen, alkyl, alkoxy, halogen, hydroxy, acyloxy or optionally substituted arylsulfonyloxy, X is hydrogen or alkyl and the double bond on the &agr; chain has E configuration or Z configuration, a pharmaceutically acceptable salt thereof or a hydrate thereof.
Through the present specification, the group of the formula in the compound of the formula (I):
wherein X is as defined above,
is referred to as &agr; chain and the group of the formula:
wherein R is as defined above,
is referred to as &ohgr; chain.
The double bond on the &agr; chain has E configuration or Z configuration.
In detail, examples of the above compound include a compound of the formula (IA):
wherein R and X are as defined above and the double bond on the &agr; chain has E configuration or Z configuration, and a compound of the formula (IB):
wherein R and X are as defined above and the double bond on the &agr; chain has E configuration or Z configuration.
In more detail, the compound of the formula (IA) includes a compound of the formula:
wherein R and X are as defined above and the double bond on the &agr; chain has E configuration or Z configuration.
Preferred is the compound of the formula (IA-a), (IA-b), (IA-c), (IA-d) or (IA-b′). Especially preferred is the compound of the formula (IA-a).
The compound of the formula (IB) includes a compound of the formula:
wherein R and X are as defined above and the double bond on the &agr; chain has E configuration or Z configuration.
Preferred is the compound of the formula (IB-a′) or (IB-b′).
Among the above examples, preferred is a compound wherein the double bond on the &agr; chain has E configuration, a compound wherein the double bond on the &agr; chain has Z configuration, a compound wherein R is hydrogen, methyl, methoxy, bromo, fluoro, hydroxy, acetoxy or phenylsulfonyloxy and X is hydrogen or a compound wherein R is hydroxy and X is hydrogen.
Preferred is a compound of the formula (IA-a-5):
A preferred PGD
2
receptor antagonist has a high PGD
2
antagonistic activity and a high selectivity. Another preferred has a low agonistic activity. For example, a preferred antagonist has a PGD
2
binding inhibitory activity (IC
50
valu
Fay Zohreh
Foley & Lardner
Kwon Brian-Yong S.
Shionogi & Co. Ltd.
LandOfFree
Methods for the treatment of itching comprising... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods for the treatment of itching comprising..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods for the treatment of itching comprising... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3026886