Method of treating chronic abacterial prostatitis with selective modulators of estrogen receptors or aromatase inhibitors

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology, and can be used for treatment of chronic abacterial prostatitis in men, which is not connected with dysfunction of urethral sphincter. For this purpose, efficient amount of fispemiphene is introduced to patient who needs it. Introduction of fispemiphene is performed in amount in the range from 0.1 to approximately 100 mg/kg of body weight.

EFFECT: invention ensures efficient treatment of abacterial prostatitis at the early stage of disease where only histological changes of prostate gland are present without presence of urethral sphincter dysfunction, with drug fispemiphene, which demonstrates antagonistic activity to estrogen receptors in particular with respect to prostate tissue.

2 cl

 

BACKGROUND of INVENTION

The technical field to which the invention relates.

The invention relates to a method for the treatment of men suffering from chronic abacterial prostatitis, a selective modulator of estrogen receptor (SERM), an aromatase inhibitor and/or antiestrogen.

DESCRIPTION of the PRIOR art,

Prostatitis is an inflammatory disease of prostate, which affects about 50 percent of all men in some periods of life. Chronic abacterial prostatitis is the inflammation involved the prostate gland that usually affects men of all ages. This can cause chronic pelvic pain syndrome (CPPS), problems with urination, including discomfort and pain, increased urinary frequency and urgency, or problems associated with the release of the bladder.

In the appropriate hormonal environment with the presence of androgens chronic abacterial prostatitis can progress to hypertrophy of the prostate (benign prostatic hyperplasia (BPH)and prostate cancer.

Selective modulators of estrogen receptors (SERM) are compounds that bind to estrogen receptors in various tissues, but with both antagonistic and agonistic activities. Compounds such as tamoxifen, toremifene, raloc even, lasofoxifene, bazedoxifene, ospemifene and fispemifene are typical SERM. They have some common characteristics, such as anti-estrogenic activity in breast cancer and estrogenic activity in bone, whereas in other organs, they demonstrate varying degrees estrogenic or antiestrogenic properties. In the urinary tract, apparently, is dominated by antiestrogenic properties.

Experimental models have shown that selective modulators of estrogen receptor (SERM) may be useful for the treatment or prevention of symptoms of the lower urinary tract (LUTS). Method for the treatment or prevention of symptoms of the lower urinary tract, including bacterially prostatitis, using a SERM is fully disclosed in the patent application US No. 10/454823 included in the description by reference, in US patent No. 5972921 included in the description by reference, describes the treatment with aromatase inhibitors dysfunction urethral sphincter, causing LUTS.

The basis for treating the symptoms of the urinary tract using a SERM or aromatase inhibitors is the observation that the increase in the ratio of estradiol to testosterone leads to the development of dysfunction of the urethral sphincter, which causes LUTS. However, although chronic abacterial prostatitis pelvic pain can sometimes be a Saint who is associated with the dysfunction of the urethral sphincter, not previously assumed estrogenization the cause of chronic bacteriologi prostatitis.

Men obstruction of the urethra due to benign prostate hyperplasia (BPH), benign prostate hyperplasia, as is often assumed, is the main cause of LUTS. However, several studies have shown that there is only a weak correlation between prostatic hypertrophy, obstruction and LUTS.

The INVENTION

Now believe that chronic abacterial prostatitis is estrogenozavisimymi. Elevated levels of estrogen in relation to the concentration of androgen in adult noble rats causes abacterial prostatitis as a direct effect on the prostate without simultaneous dysfunction of the urethral sphincter. Prostatitis in rats installed by monitoring cell inflammation zone, and histologically detected that the same process occurs in men.

Therefore, the present invention is a method of treating chronic bacteriologi prostatitis in men, in which chronic abacterial prostatitis is not associated with dysfunction of the urethral sphincter. The method includes introducing an effective amount of (i) a selective modulator of estrogen receptor with anti-estrogenic effect on the prostate, (ii) aromatase inhibitor and/or (iii antiestrogen, if the subject requires it.

The invention is also a method of preventing progression of BPH and prostate cancer. The development of stromal razresheniya (homologous stromal hypertrophy with BPH in humans) and the development of prostate cancer associated with a long period of chronic prostatitis. Treatment of chronic prostatitis using a SERM, such as fispemifene, or an aromatase inhibitor or antiestrogen will prevent the progression of BPH or prostate cancer.

DETAILED description of the INVENTION

The inventors found that a SERM such as fispemifene, counteract the effects of estrogen on the prostate and can thus be used to prevent or treat chronic bacteriologi prostatitis. Similarly, the decrease in the concentration of estrogen in the body by use of aromatase inhibitors, or when the use of an antiestrogen can be used to treat this condition.

To show the effect of the increased amount of estrogen relative to testosterone in chronic abacterial prostatitis, the first group of noble rats were treated for 6 weeks with testosterone (T) (240 mg/day) and estradiol (E2) (70 g/day)to create animals profile normal T/high E2 (the ratio of T/E2 was 30 in the test group compared with 150 in the control group; the end of the filtration T was 0.8 ng/ml compared with 1.5 in the control group; the concentration of E2-30 PG/ml compared to 10 PG/ml in the control group). Animals found bacterially prostatitis in the absence of difficult urination and normal size of the prostate.

To show the effect of a higher ratio of estradiol in an environment with a low level of testosterone, noble rats treated for 13 weeks T (240 mg/day) and E2 (70 g/day), showing the low profile of the ratio T/high E2 (the ratio of T/E2 was 1:10 in the test group compared with 150 in the control group; the concentration of testosterone was 100 PG/ml compared to 1.5 ng/ml in the control group; the concentration of estradiol was 40-80 PG/ml compared to 10 PG/ml in the control group). Animals in this group was diagnosed with chronic abacterial prostatitis without significant urodynamic changes and again in the absence of difficult urination. Animals found unaugmented the prostate, but with the proliferation of stroma, such as benign hyperplasia of the prostate in men.

To demonstrate the impact of the increased ratio of estradiol to testosterone in the context of an environment with high levels of testosterone, the third group of noble rats treated for 13 weeks with T (800 mcg/day) and E2 (70 g/day). The ratio of T/E2 was 75 in the test group compared with 150 in the control of the GRU is PE. Testosterone concentration was 4.5 ng/ml in the test group compared with 1.5 ng/ml in the control group. Estradiol concentration was 60 PG/ml compared to 10 PG/ml in the control group. The prostate of these animals was more normal, demonstrating chronic prostatitis and pre-malignant lesions and ductal carcinoma of the prostate, leading to the idea of the trend toward the development of BPH and prostate cancer.

To demonstrate the use of an antagonist of estrogen for the treatment of chronic bacteriologi prostatitis, the fourth group of rats were treated for 3 weeks with T (240 mg/day) and E2 (70 g/day), after which it was administered 2 doses of pure antagonist of estrogen fulvestrant (5 mg/kg) on the third week. Fulvestrant significantly reduced the symptoms of prostatitis in comparison with the control group that was treated only with T and E2. Since prostatitis is possible to reverse the appointment of the antiestrogen, the state looks estrogenozavisimymi.

To demonstrate the effect of the antagonist of the estrogen fispemifene on the prostate, the fifth group of noble rats castrated and treated with fispemifene for three weeks at doses of 3, 10 and 30 mg/kg with concomitant appointment of estradiol (70 g/day), and without it. It was observed that fispemifene was the antagonist of estrogen for prostate and dose-dependently inhibited in Sodeistvie estradiol on the prostate, measured FRA2 or PR expression, which are sensitive markers to the effects of estrogen.

I believe that the dose of 0.1 to 100 mg/kg fispemifene (or other SERM), administered to males different routes of administration, including, without limitation, oral, topical, transdermal or subcutaneous route of administration, will affect the prostate as an estrogen antagonist for the treatment of chronic bacteriologi prostatitis and/or prevent the development of BPH and prostate cancer. The preferred range of dosage from about 0.1 to about 10.0 mg/kg, with an expected daily dosage in the range of about 100 mg to about 300 mg per person. I believe that the oral route of administration is most preferred. Suitable dosage forms include, for example, tablets, capsules, granules, powders, suspensions and syrups.

1. A method of treating chronic bacteriologi prostatitis in men, including placing a patient in need, an effective amount of fispemifene where specified chronic abacterial prostatitis is not associated with dysfunction of the urethral sphincter.

2. The method according to claim 1, comprising a stage of introduction of fispemifene in amounts ranging from about 0.1 to about 100 mg/kg of body weight.



 

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