Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
1999-10-18
2001-10-16
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S912000
Reexamination Certificate
active
06303655
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition which is useful as an agent for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells.
More particularly, the present invention relates to an agent for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells, which comprises as the active ingredient N-(3,4-dimethoxy-cinnamoyl)anthranilic acid (generic name: Tranilast) represented by the formula:
or a pharmaceutically acceptable salt thereof.
In the present invention, as diseases associated with excessive proliferation of retinal pigment epithelial cells, proliferative vitreoretinopathy can be exemplified.
BACKGROUND OF THE INVENTION
In surgical retinopexy performed as a remedy for retinal detachment, proliferative vitreoretinopathy, a disease associated with excessive proliferation of retinal pigment epithelial cells, is known to remain as a cause of worsening prognosis. At the present time, only vitreous surgery has been used as a remedy for such proliferative vitreoretinopathy. Under present conditions, visual prognosis is not necessarily said to be favorable even after the surgery. It is well known that the proliferation of retinal pigment epithelial cells plays an important role in the occurrence and development of such proliferative vitreoretinopathy. Many researchers have studied the inhibitory effects of various drugs on proliferation of retinal pigment epithelial cells (Japanese Review of Clinical Ophthalmology, Vol. 9, pp. 1886-1890 (1993); Japanese Review of Clinical Ophthalmology, Vol. 9, pp. 2030-2034 (1993).
On the other hand, the technical progress of vitreous surgery has resulted in remarkable improvements in the cure rate of retinal detachment. However, a limit of the cure rate is said to be 92-94%. It is thought that proliferative vitreoretinopathy, namely, proliferation of retinal pigment epithelial cells largely participates as the cause of limiting the cure rate. Therefore, development of drugs having excellent inhibitory effects on excessive proliferation or retinal pigment epithelial cells have been desired to improve the cure rate of retinopexy for retinal detachment and for the prevention or treatment of proliferative vitreoretinopathy.
Tranilast has been used widely as a drug for the treatment of allergic disorders such as bronchial asthma, allergic rhinitis, atopic dermatitis and allergic conjunctivitis, and cutaneous disorders such as keloid and hypertrophic scar. For example, it has been known that Tranilast has inhibitory effects on chemical mediator release caused by an allergic reaction, excessive collagen accumulation by fibroblast cells in cutaneous tissues and excessive proliferation of smooth muscle cells in coronary artery vessels.
However, it has not been disclosed that Tranilast suppresses proliferation of retinal pigment epithelial cells and is therefore useful as an agent for the prevention or treatment of proliferative vitreoretinopathy.
SUMMARY OF THE INVENTION
The present invention relates to an agent for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells, which comprises as the active ingredient N-(3,4-dimethoxy-cinnamoyl)anthranilic acid represented by the formula:
or a pharmaceutically acceptable salt thereof.
The present invention relates to a method for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells, which comprises administering N-(3,4-dimethoxycinnamoyl)anthranilic acid represented by the above formula (I) or a pharmaceutically acceptable salt thereof.
The present invention relates to a use of N-(3,4-dimethoxycinnamoyl)anthranilic acid represented by the above formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition for the prevention and treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells.
Furthermore, the present invention relates to a use of N-(3,4-dimethoxycinnamoyl)anthranilic acid represented by the above formula (I) or a pharmaceutically acceptable salt thereof as an agent for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells.
The present inventors have studied earnestly to find compounds having inhibitory effects on excessive proliferation of retinal pigment epithelial cells. As a result, it was found that Tranilast has a marked inhibitory effect on proliferation of retinal pigment epithelial cells, and therefore, is extremely useful as an agent for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells, thereby forming the basis of the present invention.
Accordingly, the present inventors confirmed that Tranilast markedly suppressed proliferation of retinal pigment epithelial cells in the in vitro cell proliferation inhibitory effect test using rat retinal pigment epithelial cells.
DETAILED DESCRIPTION OF THE INVENTION
Tranilast has been found to provide an excellent inhibitory effect on proliferation of retinal pigment epithelial cells, and therefore, is a compound useful as an agent for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells.
Therefore, pharmaceutical compositions which are useful as agents for the prevention or treatment of diseases associated with excessive proliferation of retinal pigment epithelial cells can be prepared by comprising as the active ingredient Tranilast or a pharmaceutically acceptable salt thereof.
Various methods for the preparation of Tranilast and pharmaceutically acceptable salts thereof which are active ingredients are known, and they can be readily prepared by methods described in patent literature and the like (Japanese Patent Application Publication (kokoku) No. Sho. 56-40710; ibid. No. Sho. 57-36905; ibid. No. Sho. 58-17186; ibid. No. Sho. 58-48545; ibid. No. Sho. 58-55138; ibid. No. Sho. 58-55139; ibid. No. Hei. 1-28013; ibid. No. Hei. 1-50219; ibid. No. Hei. 3-37539 etc.).
As examples of pharmaceutically acceptable salts of Tranilast, salts with inorganic bases such as a sodium salt and a potassium salt, salts formed with organic amines such as morpholine, piperidine, piperazine and pyrrolidine and salts formed with amino acids can be illustrated.
When the pharmaceutical compositions of the present invention are employed in a practical treatment, the composition may be administered orally. A topical administration such as eye drops, eye ointments or injections is preferable.
For example, eye drops can be formulated by dissolving Tranilast or a pharmaceutically acceptable salt thereof together with a basic substance with heating in a proper quantity of sterilized water in which a surface active agent is dissolved, adding polyvinylpyrrolidone, and optionally adding appropriate pharmaceutical additives such as a preservative, a stabilizing agent, a buffer, an isotonicity, an antioxidant and a viscosity improver, and dissolving the additives completely.
For example, eye ointments can be appropriately formulated by using bases which are generally used in eye ointments. Eye ointments can be also used as reversible thermally gelling water-base pharmaceutical compositions.
For example, injections can be injected directly into diseased tissues such as vitreous or adjacent tissues by using a fine needle, and can be also used as intraocular perfusate.
The pharmaceutical compositions of the present invention can be administered as sustained release preparations. For example, a Tranilast preparation can be incorporated into a pellet or microcapsule of sustained release polymer as a sustained release preparation, and the pellet or microcapsule surgically implanted into the tissues to be treated. As examples of sustained release polymers, ethylene-vinylacatate copolymer, polyhydro-methacrylate, polyacrylamide, polyvi
Kitazawa Makio
Takehana Yasuo
Fay Zohreh
Frenkel Stuart D.
Kissei Pharmaceutical Co. Ltd.
Liniak Berenato Longacre & White
LandOfFree
Preventives or remedies for diseases affecting excessive... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Preventives or remedies for diseases affecting excessive..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Preventives or remedies for diseases affecting excessive... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2604738