Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1996-09-27
1998-06-23
Jarvis, William R. A.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
A61K 3158
Patent
active
057705895
DESCRIPTION:
BRIEF SUMMARY
This application claims priority under 35 U.S.C. 371 to PCT/AU94/00424, filed Jul. 27, 1994.
TECHNICAL FIELD
The present invention relates to the treatment of inflammatory response in the macula of the eye.sup.1,2,3,4,5,6 by use of a depot injection into the vitreous humour of a suitable anti-inflammatory agent. In particular it relates to the treatment of age-related macular degeneration and more particularly relates to the treatment of the end stage of this condition with anti-inflammatory steroids. This end stage previously has been presumed to be untreatable.
BACKGROUND ART
The major cause of registrable blindness in developed countries is due to the condition known as age-related macular degeneration.sup.7. In this condition, the macula which is a minute area in the centre of the retina is damaged. The macula occupies a total area of less than 1 mm.sup.2. This area is especially adapted for acute and detailed vision. In the central portion of the macula, known as the fovea (which is 0.4 mm in diameter) the blood vessels, and other cells are displaced to the side, allowing light to fall onto the photosensitive layer. This is in contrast to other parts of the retina where light has to pass through several layers of tissue before arriving at the photosensitive layer.
The condition itself is conveniently divided into three stages. It may present as early stage macular degeneration. At least 20% of patients develop an active neurovascular form.
One end stage of this condition is known as atrophic macular degeneration (AMD) while a second end stage is known as neovascular macular degeneration (NMD), which is caused when new blood vessels begin to grow under the retina, particularly the macula.
AMD is not treatable, whereas NMD in some cases may be relieved by laser treatment. However, a complication of laser treatment is actual loss of vision. In addition, laser treatment, where applicable, is not always a permanent cure since the blood vessels may begin to grow again.
The problem of macular degeneration is immense. It has been estimated that 25% of people 70 and over in the developed world will have the mild form of the condition while 1 in 10 have severe symptoms and 1 in 100 progress to complete blindness.
The present inventors have recently demonstrated that intravitreal injection of an anti-inflammatory steroid in depot form substantially arrests and/or reverses AMD and NMD.
It has been shown.sup.8,9 that intravitreal administration of anti-inflammatory steroids inhibits vascular proliferation in the eye. The inventors have shown.sup.1,2,3,4,5 in human patients that AMD is promoted by choroidally derived inflammatory cells. The inventors recently described resident immunocompetent cells.sup.5 in the neural retina which would be subject to the influence of intravitreal anti-inflammatory steroids.
DISCLOSURE OF THE INVENTION
According to a first form of this invention there is provided a method for the treatment or prophylaxis of macular degeneration in a patient requiring said treatment or prophylaxis, comprising administering by intravitreal injection to said patient an effective amount in depot form of an anti-inflammatory steroid which is preferably sparingly soluble in the vitreous,
Preferred steroids include 11-substituted 16.alpha.,17.alpha.-substituted methylenedioxy steroids of the formula ##STR1## R.sub.1 and R.sub.2 are hydrogen or alkyl; ##STR2## R.sub.3 is methyl, hydroxymethyl or alkylcarbonyloxymethyl, methylaminoalkylenecarbonyloxymethyl, or phenylamino alkylenecarbonyloxymethyl; R.sub.4 is alkanoyl; and X is halogen.
More preferred are compounds of the formula ##STR3## wherein R.sub.3 is hydroxymethyl, phenylcarbonylaminoisopropylcarbonyloxymethyl, or 2,2-dimethylpropylcarbonyloxymethyl.
The preferred steroid is crystalline e-3,20-dione: ##STR4##
This compound, also known by its generic name as triamcinolone acetonide is suitably prepared by known methods.sup.10,11,12,13.
The steroids are preferably crystalline and are administered in distilled water with a minimum of carriers o
REFERENCES:
Chandler et al, Chemical Abstracts, vol. 107, abstract No. 229394, 1987.
Billson Francis Alfred
Penfold Philip Leslie
Jarvis William R. A.
The University of Sydney
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