Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1997-10-20
2001-08-28
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...
C514S912000
Reexamination Certificate
active
06281224
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a pranoprofen ophthalmic solution containing an organic amine, and the ophthalmic solution is characterized in that a change in the composition thereof does not occur, the stability is excellent and irritation is little.
BACKGROUND TECHNIQUES
Pranoprofen is an acidic non-steroidal anti-inflammatory drug which is a propionic acid derivative, is useful for inflammatory diseases in the ophthalmic field such as keratoconjunctivitis in an extraocular area and an anterior segment of the eye, and has been put into practice in the form of an ophthalmic soluton. Pranoprofen can stimulate the eyes and, therefore, a variety of attempts have been made to suppress the irritation in order to prepare ophthalmic solutions. For example, there have been proposed a method by addition of boric acid (Japanese Laid-open Patent Publication No. 60-184013), a method by addition of carbonate (Japanese Laid-open Patent Publication No. 5-186349) and a method by addition of acetate ion (Japanese Laid-open Patent Publication No. 7-17863)to reduce such irritation.
On the other hand, an attempt at preparing ophthalmic solutions and intraocular Irrigating solutions containing an organic amine have been also made. For example, in a case of an ophthalmic solution containing sulfa drugs, there has been disclosed a method for making it possible to solubilize sulfa drugs and enhancing the preserative properties by addition of an alkanolamine such as monoethanolamine, diethanolamine or triethanolamine in ophthalmic solutions containing a sulfa drug and, thereby, (Japanese Patent Publication No. 1-29170, Japanese Laid-open Patent Publication No. 59-89616 and Japanese Laid-open Patent Publication No. 61-12617). In addition, there have been also disclosed diclofenac sodium ophthalmic solutions containing tromethamine or a homologue thereof having 10 or less carbon atoms as preseratives and a stabilizing agent (Japanese Laid-open Patent Publication No. 62-242617, Japanese Laid-open Patent Publication No. 62-242618), and intraocular irrigating solutions containing chondroitin sulfate in which 4-(2-hydroxyethyl)-1-(2-sulfoethyl)piperazine (hereinafter referred to as “HEPES”) is formulated (PCT WO87/00753 and U.S. Pat. No. 4725586).
However, there has not been reported yet preparations of ophthalmic solutions containing pranoprofen as an active ingredient and in which an organic amine is formulated.
It is an interesting theme to find ophthalmic solutions containing pranoprofen as an active ingredient, which has an excellent stability and little irritation to eyes.
An object of the present invention is to provide ophthalmic solutions containing pranoprofen as an active ingredient, which has no change in the composition, an excellent stability and little irritation to eyes.
In order to find pranoprofen ophthalmic solutions having an excellent stability and little irritation to eyes, the present inventors studied extensively. As a result, the present inventors found that ophthalmic solutions which have no change in the composition, an excellent stability and little Irritation to eyes can be prepared by addition of an organic amine such as tromethamine or HEPES.
SUMMARY OF THE INVENTION
The present invention relates to an ophthalmic solution containing pranoprofen as an active ingredient, in which an organic amine is formulated (hereinafter referred to as “the present ophthalmic solution”).
Preferred organic amines used in the present ophthalmic solution is alkanolamines such as tromethamine, monoethanolamine, diethanolamine and triethanolamine; sulfoalkyl piperazines such as HEPES, 1,4-bis(2-sulfoethyl)piperazine (hereinafter referred to as “PIPES”), 1,4-bis(3-sulfopropyl)piperazine (hereinafter referred to as “PIPPS”) and 1,4-bis(4-sulfobutyl)piperazine (hereinafter referred to as “PIPBS”); sulfoalkyl alkylenediamines such as N,N′-bis(3-sulfopropyl)ethylenediamine (hereinafter referred to as “EDPS”). Tromethamine and HEPES are particularly preferable.
The concentration of the organic amine to be used can be appropriately selected and, in a case of tromethamine and HEPES, 0.1 to 5.0%, inter alia, 0.5 to 2.5%, particularly 2.0% is preferable.
The concentration of pranoprofen which is an active ingredient in the present ophthalmic solution to be used can be appropriately selected depending upon symptoms and 0.01 to 0.5%, particularly 0.1% is preferable.
Additionally, preseratives are formulated in the present ophthalmic solution, if necessary. Presertives widely used in the ophthalmic solutions can be used and, in particular, benzalkonium chloride is preferable and the concentration thereof to be used is preferably 0.002 to 0.01%, more preferably 0.005%.
The pH of the present ophthalmic solution can be in a range which is acceptable to ophthalmic preparations, and a range of 6.5 to 8.5 is preferable and a range of 7.6 to 8.0 is particularly preferable in viewpoint of the eye irritating properties.
As used herein, the concentration of each ingredient in the present invention is expressed as % by weight (w/v).
Pranoprofen is useful for inflammatory diseases in the ophthalmic field such as keratoconjunctivitis in an extraocular area and an anterior segment of the eye, and has been put into practice in the form of an ophthalmic solution. Pranoprofen causes ocular pain because of irritation to eyes. In order to suppress the irritation, a variety of attempts have been made (Japanese Laid-open Patent Publication No. 60-184013, Japanese Laid-open Patent Publication No. 5-186349, Japanese Laid-open Patent Publication No. 7-17863). Further, there is a demand for development of ophthalmic solutions having reduce irritating properties.
On the other hand, there have been disclosed sulfa drug-containing ophthalmic solutions which contain an organic amine (Japanese Patent Publication No. 1-29170, Japanese Laid-open Patent Publication No. 59-89616, Japanese Laid-open Patent Publication No. 61-12617), diclofenac sodium ophthalmic solutions (Japanese Laid-open Patent Publication No. 62-242617, Japanese Laid-open Patent Publication No. 62-242618) and intraocular irrigating solution containing chondroitin sulfate (PCT WO87/00753, U.S. Pat. No. 4,725,586). However, heretofore there has been no report on pranoprofen ophthalmic solutions containing an organic amine.
Then, in order to find pranoprofen ophthalmic solutions having an excellent stability and little irritation to eyes, the present inventors extensively studied preparations containing an organic amine.
As a result, as detailed data will be shown in the Examples hereinbelow and the section entitled “Effect of the invention”, it was found that the present ophthalmic solution has no change in the composition, a high pranoprofen remaining rate, no pH change, and reduced eye irritation properties and, thus, is useful as an ophthalmic solution having pranoprofen as an active ingredient.
A general process for preparation of the present ophthalmic solution is as follows: An organic amine is added to sterile purified water, and pranoprofen is added thereto while stirring to completely dissolve it. To this is added a preserative to dissolve it, the pH is adjusted with hydrochloric acid or sodium hydroxide, and the solution is finally sterilized by filtration to obtain the present ophthalmic solution.
In addition, isotonic agents such as sodium chloride and concentrated glycerin, non-ionic surfactants such as polyoxyethylene sorbitan monooleate (hereinafter referred to as “polysorbate 80”), stearic polyoxyl 40 and polyoxyethylene hydrogenated castor oil, stabilizing agents such as sodium edetate and sodium citrate can be added thereto together with the organic amine, as necessary.
REFERENCES:
patent: 4725586 (1988-02-01), Lindstrom et al.
patent: 4829083 (1989-05-01), Doulakas
patent: 4829088 (1989-05-01), Doulakas
patent: 5414011 (1995-05-01), Fu et al.
patent: 59-89616 (1984-05-01), None
patent: 61-12617 (1986-01-01), None
patent: 62-242618 (1987-10-01), None
patent: 62-242617 (1987-10-01), None
patent: 1-29170 (1989-06-01), None
patent: 2-
Horibe Yoshihide
Miyagi Shogo
Fay Zohreh
Frishauf, Holtz Goodman, Langer & Chick, P.C.
Santen Pharmaceutical Co. Ltd.
LandOfFree
Pranoprofen eyedrops containing organic amine does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pranoprofen eyedrops containing organic amine, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pranoprofen eyedrops containing organic amine will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2501828