Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1997-05-12
1998-06-02
Fay, Zohreh
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
514573, 514912, A61K 31215, A61K 3119
Patent
active
057600759
DESCRIPTION:
BRIEF SUMMARY
Secondary cataract is a condition characterized by opacification of the posterior lens capsule after cataract surgery. The opacification usually becomes manifest 2-10 years after surgery, but the formation of secondary cataract in young children may be much quicker. When the lens with age or due to different pathological conditions becomes opaque cataract ensues. There are many kinds of cataract depending on the cause of the opacification. So far cataract can only be treated surgically by removing the lens. The cataractous lens can be removed with the capsule in its entirety which is called intracapsular cataract extraction. Presently, however, a more common procedure is to remove the lens with part of its anterior capsule only, thus leaving the posterior lens capsule in the eye intact. This procedure is called extracapsular cataract extraction. In such eyes usually an intraocular artificial lens is implanted into the remaining lens capsule bag and in most cases good vision is restored.
A problem, however, is that in the extracapsular cataract extraction technique with implantation of an artificial lens into the eye, remnants of the lens, its epithelium, and possibly also other cells are commonly not completely removed. Frequently these tissue remnants slowly starts to proliferate and with time tend to opacify the posterior lens capsule so that vision is impaired. This condition is, as mentioned above, called secondary cataract. After ordinary uneventful extracapsular cataract surgery secondary cataract develops to a point when it interferes with functional vision, usually within 2-10 years, but it may be faster and in some cases may not develop at all.
A number of different ways to prevent secondary cataract have been suggested over the years, both with regard to the intraocular lens as such and the technique used in surgery. So has for instance Hoffer in U.S. Pat. No. 4,244,060 described a lens that has a barrier ridge on the side facing the capsule wall. The intention was to create a mechanical barrier inhibiting migration of residual lens epithelial cells and their derivatives into the optical zone behind the IOL.
Administration of various types of drugs during surgery for preventing opacification is another approach that has been found to be of potential importance. Examples of such drugs are colchicine and 5-fluorouracil.
Colchicine is a mitosis-inhibiting phenanthrene derivative isolated from Colchicum autumnale. Colchicine arrests mitosis at metaphase by binding to a protein present in microtubules, hence interfering with the structure of the mitotic spindle. The substance has been shown to be a potent inhibitor of lens epithelial cell proliferation and migration. However, colchicine has a low therapeutic index with a lot of potential side effects, including a temporary toxic effect on the optic nerve when used for preventing posterior capsule opacification in primates.
5-Fluorouracil is a potent anti mitotic drug affecting the DNA replication and is widely used in the treatment of epithelial tumours. Ruitz et al (Inhibition of posterior capsule opacification by 5-fluorouracil in rabbit; Ophthalmic Res. 22 (1990) 201-208) have also shown that this substance reduces posterior capsule opacification in vivo in rabbits.
Even if there are reports claiming the potential use of drugs of the type mentioned above, currently the only reasonably successful way to clinically treat secondary cataract is by performing a capsulatomy. This can be done surgically but is usually carried out by a YAG-laser. Generally the result of such YAG-laser capsulotomy is good and in most cases good functional vision is restored. However, a problem with this procedure is that complications in the posterior segment of the eye may ensue. Such complications comprise e.g. macular edema. It seems reasonable to believe that also in cases of very qualified surgery there might be some remnant cells in the capsular bag forming a potential basis for cell attachment and growth in the optic area of the posterior capsule, even if delayed to
Resul Bahram
Stjernschantz Johan
Fay Zohreh
Pharmacia & UpJohn AB
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