Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1997-12-19
2000-03-28
Fay, Zohreh
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514912, A61K 3700
Patent
active
060432136
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention provides a pharmaceutical composition comprising albumin as an active ingredient. The composition of the present invention is useful for treatment of the conditions such as corneal and conjunctival lesion and dry eye. The composition of the present invention has an ability to increase eye surface epithelium mucin secretion and also has an ability to diffuse oil. The present invention further provides methods for treatment of corneal and conjunctival lesion, treatment of dry eye conditions, and increase of eye surface epithelium mucin secretion using the composition.
BACKGROUND ART
Corneal and conjunctival lesion is caused by forming defects from the surface to epithelium. The cause may include pathogenic factors such as keratoconjunctivitis sicca (dry eye), various keratoconjunctivitis, allergy and infection of microorganisms (e.g. virus, bacteria, fungus, etc.), chemical factors such as cytotoxicity by chemicals and corrosion due to acid and alkaline, physical factors such as xerophthalmia, injury due to foreign matter (e.g. contact lens, etc.) and hot water, and the like. It has recently been reported that antiseptics contained in an ophthalmic composition (e.g. benzalkonium chloride, chlorobutanol, etc.) and ophthalmic agents (e.g. aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs, IDU, pimaricin, etc.) cause a lesion of corneal epithelium (ectocornea).
For the present, in order to treat the corneal and conjunctival lesion, chondroitin sulfate, glutathione, hyaluronic acid, fibronectin, EGF, and the like are administered or an artificial tear solution is also administered for the purpose of replenishing a tear solution, but the effect of these treatments is not yet sufficient.
Dry eye is defined as a condition with decrease or change in quality of tear, irrespective of the presence or absence of corneal and conjunctival lesion (Yamada et al. GANKI 43, 1289-1293(1992)). There are various factors for causing the dry eye, but no suitable method to recover the decreased amount of tear normal has been found yet.
For the present, in order to treat the dry eye, an artificial tear solution for the purpose of replenishing tear, and chondroitin sulfate, glutathione, hyaluronic acid, fibronectin, EGF, and the like for the purpose of relieving subjective symptoms are administered, but the effects are not yet sufficient.
From the recent investigation, it is believed that normal eye surface epithelium expresses mucin-like glycoproein and that said glycoprotein takes an active part in maintaining tear film. Furthermore, mucin secreted from conjunctival germ cells has been known to be responsible to stabilize tear film. So, defect of eye surface epithelium caused by any factor may induce abnormal eye mucin secretion and thereby unstable tear film. The unstable tear film may lower the interaction level between the epithelium and the tear film, and thereby the lesion of corneal and conjunctival epithelium may become worse (Norihiko Yokoi in "GANKA CHIRYO NO KOTSU TO OTOSHIANA" (Techniques for treatment in Ophthalmologic field), edited by FUMIO KOGURE, published by KABUSHIKI KAISHA NAKAYAMA SHOTEN, Tokyo, Japan pages 26-27 (1995)). From these points of view, it is suggested that conditions such as corneal and conjunctival lesion or dry eye can be treated if the tear film is stabilized by increasing mucin secretion or any other mean.
Albumin is a protein that exists widely in an animal/vegetable tissue or a body fluid, such as human serum, tear solution. For example, the human serum albumin is used for treating hypoalbuminemia, hemorrhagic shock, and the like. In the ophthalmic field, it is also known to use as a stabilizer for protein preparations such as fibronectin or interferon. It has been proposed to use the preparations such as fibronectin and interferon for treating corneal lesion (Japanese Patent Kokai No. Sho 61-103838 and No. Hei 6-271478), but there is no knowledge that albumin itself is effective for treating corneal and conjunctival lesion or dry eye.
REFERENCES:
patent: 4775531 (1988-10-01), Gilbard
Chemical Abstracts 122: 38840. Tsuboto et al, 1994.
Database Drugu, AN 84-16297. Koning et al. Combination Therapy for Dendritic Keratitis with Acyclovir and Alpha--Interferon. Arch. Ophthalmol. 101(12), 1866-68 (Dec. 1983).
Gupta et al. Trypsin and Serum Albumin in Tear Fluids in Acute Adenovirus Conjunctivitis. BR. J. Ophthalmol 72(5), 390-393 (May 1988).
Pedersen et al. The origin of immunoglobulin G in bovine tears. Acata Path. Microbiol.Scand.Set.B, 81B/2, 245-252 (Feb. 1973).
Zavaro et al. Proteins in Tears from Healthy and Diseased Eyes. Symposium on Uveal Melanomes, Nov. 24, 1979. Doc Ophthalmol 50(1) (Recd. 1981). 185-199 (Jan. 1981).
Ran S et al. Topical Plasma Fibronectin Compared to Albumin and Saline for Wond Healing of Denervated Corneal Epithelial Defeacts. Annual Spring Meeting of Association for Research in Vision and Ophthalmology, Sarasotata, Florida, USA, Apr. 3. (Mar. 1989).
Fay Zohreh
R-Tech Ueno Ltd.
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