Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
2001-09-17
2004-05-11
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S452000, C424S464000, C424S465000, C424S489000, C424S490000, C424S491000
Reexamination Certificate
active
06733779
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to methods for treating benign prostate hyperplasia and reducing the level of prostate specific antigen of benign prostate conditions. More specifically, the methods utilize 13 cis-retinoic acid to effectively treat benign prostate hyperplasia, and to reduce the level of prostate specific antigen of the patients with benign prostate conditions.
BACKGROUND OF THE INVENTION
The three most common prostate health problems facing men and their families today are benign prostatic hyperplasia (BPH), prostate cancer, and prostatitis. Each of these conditions affects the prostate differently. Benign prostate hyperplasia is the most common benign neoplasm (non cancerous enlargement of the prostate gland) in men, and has a high prevalence that increases with age. The increase in size of the prostate inside its capsule exerts pressure on the urethra, which passes through the capsule, resulting in obstruction to urine flow. Half of all men have BPH identifiable histologically at age 60 years, and by 85 years the prevalence is about 90%. In the United States about 25% of men will be treated for BPH by age 80, and over 300,000 surgical procedures are performed each year for BPH (mostly transurethral resection of the prostate, TURP). This makes TURP the second most common surgical procedure, second only to cataract surgery—at a cost estimated at $2 billion per year. Experts do not yet know what causes BPH, but the condition may be related to the hormone testosterone and its relationship to other hormones that change during the aging process.
There are a number of treatment options for BPH. These include watchful waiting, medical therapy such as alpha blocker therapy and finasteride therapy, balloon dilatation and various surgical procedures such as transurethral incision of the prostate (TUIP), transurethral resection of the prostate (TURP), and open prostatectomy. Few treatments are without any adverse consequences, and this is particularly so with treatments with BPH, where there is a delicate balancing act between the benefits and demerits of the treatments available. The adverse events following treatment for BPH include impotence (for various surgical procedures ranging from about 4% to 40%, the incidence of impotence is also increased after some medical treatments), incontinence (stress incontinence about 3% after surgery, with total urinary incontinence approaching 1%), and the need for re-treatment. Combined analysis of published data estimated that the mean probability for perioperative mortality (death within 90 days of a procedure) was 1.5% for TURP. For open surgery it was 2.4% and for balloon dilation it was 3.5%.
It is well known that prostate specific antigen (PSA), a protein produced by prostate cells, is frequently present at elevated levels in the blood of men who have prostate cancer. The U.S. Food and Drug Administration has approved a PSA test for use in conjunction with a digital rectal exam to help detect prostate cancer in men age 50 or older and for monitoring prostate cancer patients after treatment. However, much remains unknown about the interpretation of PSA levels, the test's ability to discriminate cancer from benign prostate conditions, and the best course of action following a finding of elevated PSA. Furthermore, clinically it is known that BPH and prostatitis can cause elevated PSA.
13-cis retinoic acid, more generally known as retinoic acid, also referred to as isotretinoin, and sold under the Roche trademark Accutane, has long been known as a topical and oral dermatologic agent used in the treatment of acne vulgrais and several other skin diseases. 13-cis retinoic acid inhibits sebaceous gland function and keratinization. The exact mechanism of action of Accutane in treating acne is unknown. Since retinoic acid is a teratogneic drug and, because of the mutagenic effects associated with such drugs, it has only gradually entered the mainstream of medicine.
Experimentation in non-dermatologic applications of retinoic acid appeared in the literature in 1992 in an investigation at the University of California School of Medicine (Department of Urology), in San Francisco, this with reference to the effect of 13-cis-retinoic acid upon human prostate cancer cells. Since 1992, the research group at the University of California, headed by Dr. Dahiya, established the effect of retinoic acid in the downregulation of saturated fatty acids coupled with the upregulation of unsaturated fatty acids in human prostate cancer cells. As such, saturated fatty acids, which are believed to play a significant role in prostate cancer, were inhibited while unsaturated fatty acids, which are believed to act in a protective way relative to such cancers, were increased in cell lines.
However, isotretinoin or retinoic acid has not been used for treating benign prostate hyperplasia, or for reducing the level of prostate specific antigen of benign prostate conditions.
SUMMARY OF THE INVENTION
In one embodiment, the present invention relates to a method of treating benign prostatic hyperplasia. The method comprises the steps of (a) orally administering about 40 mg of 13-cis-retinoic acid daily for an initial treatment period from about ten days to about twenty days; and (b) thereafter orally administering about 40 mg of 13-cis-retinoic acid in about every five to seven days in a sustaining period.
In a further embodiment, the present invention relates to a method of reducing the level of prostate specific antigen (PSA) of patients. The method comprises the steps of (a) orally administering about 40 mg of 13-cis-retinoic acid daily for an initial treatment period from about ten days to about twenty days; and (b) thereafter orally administering about 40 mg of 13-cis-retinoic acid in about every five to seven days in a sustaining period.
It is accordingly an object of the present invention to provide a method of treating benign prostatic hyperplasia and related symptoms such as reduced or constricted urine stream and urinary retention.
It is another object to provide a method of reduction of the level of the prostate specific antigen of benign prostate conditions.
The above and yet other objects and advantages of the present invention will become apparent from the hereinafter set forth Detailed Description of the Invention and Claims appended herewith.
DETAILED DESCRIPTION OF THE INVENTION
The instant invention derived from the observation that the human prostate comprises a modified sebaceous gland and that, given the many years of usage of successful Accutane/isotretinoic/retinoic acid in the treatment of acne, this through the shrinking of sebaceous glands within the face and neck, that a similar action might occur upon the prostate gland if Accutane were taken as an oral medication.
Operating with the informed consent of approximately twelve patients exhibiting either or both an elevated PSA, that is, patients with a PSA of greater than 4 ng/ml and/or with exhibiting benign prostatic hyperplasia, the patients were treated with Accutane manufactured by Roche.
The treatment method involves essentially two periods: an initial treatment, and a sustaining treatment. First, in the initial treatment the patients orally administrate an initial dosage about 40 mg of 13-cis-retinoic acid daily for a period from about ten days to about twenty days. Thereafter, the patients orally administrate a sustaining dosage about 40 mg of 13-cis-retinoic acid about every five to seven days in a sustaining period. Typically, the sustaining period is about one year. However, it can be extended longer if extended maintenance is needed. Preferably, the initial treatment period is about fourteen days, because beyond fourteen days side effects of the medicine, such as tenderness at sites of old injuries to the fibro-musculo-skeletal system, dry skin, chapped lips, dry eyes, and dry nose, tend to occur. If these side effects occur during the initial treatment period, they normally subside after the sustaining dosage is instituted.
In the initial treatment, 40 m
Li Yi
Page Thurman K.
Silverman M. K.
Tran S.
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