DE3339295C2 - - Google Patents

Description

The invention relates to the use of 4-hydroxy or 4- (C₂-C₁₂) acyloxy-4-androsten-3,17-dione (s) for prophylaxis and therapy of prostate hyperplasia.

The 4-hydroxy and 4-acyloxy-4-androsten-3,17-diones are described by the following general formula I marked:

wherein R is a hydrogen atom or a 2 to 12 carbon atoms containing acyl group.

The acyl groups usually come in steroid chemistry used acyl groups in question, especially the Acetyl, heptanoyl and benzoyl group.

The compounds of general formula I are already known. They are described as aromatase inhibitors the conversion of 4-androsten-3,17-dione to estrogens inhibit human placental microsomes (Endocrinology 100 (1977) 1684-1695 and U.S. Patent 42 35 893). The Compounds can make estrogen dependent Suppress breast tumors in rats.

Prostatic hyperplasia is a benign one Enlargement of the prostate by the so-called "inner" prostate begins. The complaints are mainly due to the obstructions that occur Attributed to urethra. The bladder emptying is difficult, and there is residual urinary retention. Without surgical intervention can lead to urea poisoning come.

So far, drug treatment has been very good frequent illness in older men hardly possible. The phyto-preparations used for this purpose, such as Example β-sitosterol, mixtures of different Plant extracts and combinations of plant extracts with the neurotropic spasmolytic azoniaspirochloride proved ineffective in a one-year study. The patients felt one during the therapy Improvement of the micturition symptoms, a regression of the however, hyperplastic prostate was not achieved.

Hormones are also used in the treatment of Prostate hyperplasia; of these substances is special to call the depot gestagen gestonoron capronate. In comparison with the phyto-preparations, gestonoron capronate is used achieved a better effect. The before treatment extended micturition time is significantly reduced and the maximum flow value (urine flow in the time unit)  improved. A significant reduction in adenoma size however, it cannot be determined here either.

In US Patent 34 23 507 the treatment prostate hypertrophobia with progestogen and antiandrogen acting esters of 6-chloro-17-hydroxy-1α, 2α-methylene-pregna-4,6-diene-3,20-dions (cyproterone esters) described. However, it has been shown that only partial regression even under this treatment hyperplasia occurs.

In DE-OS 28 17 157 for prophylaxis and therapy prostate hyperplasia the use of anti-estrogens in combination with antiandrogenic substances suggested. But the use of anti-estrogens is only possible in a certain dose range, since at higher doses also anti-estrogens agonistically Estrogens).

Prostatic hyperplasia is a benign one Enlargement of the prostate, alternating Extent of interstitium (stroma) and epithelium are involved. As a cause, u. a. a shift in estrogen / Angrogenic ratio viewed in favor of estrogens will. Various studies have shown that in older men the serum testorone concentrations fall off; at the same time, the share in SHBG increases (sex hormone binding globuline, specific transport protein for steroids) so that bioavailability decreases even further in angrogens.

Since both estrogenic and androgenic factors in the Prostate hyperplasia have played a role so far proposed hormone treatments are unsatisfactory.

It has now been found that the 4-hydroxy and 4-acyloxy-4-androstene 3,17-dione of general formula I stimulation of prostate tissue. There is one Regression of the gland and to improve the micturition complaints.

There are 20 mg to 400 mg, preferably 50 mg, daily up to 250 mg of a compound of general formula I. applied.

4-Hydroxy- or 4-acetoxy-4-androsten- 3,17-dione use.

The active ingredient can be used in galenical pharmacy usual additives, carrier substances and / or flavoring agents according to methods known per se usual forms of application are processed.

For the preferred oral application come in particular Tablets, pills, capsules, pill, suspensions or Solutions in question.

For parenteral, especially intramuscular application are oily solutions, such as sesame oil or castor oil solutions. To increase solubility can be solution brokers, such as Benzyl benzoate or benzyl alcohol can be added.

Contain the medicines formulated as stated above for oral administration, preferably 10 mg to 250 mg and preferred for parenteral administration 20 mg to 200 mg 4-hydroxy-4-androsten-3,17-dione or a 4-carboxylic acid ester of 4-hydroxy-4-androsten-3,17-dione.  

Composition of tablets Example 1

20.0 mg 4-hydroxy-4-androsten-3,17-dione
130.5 mg lactose
69.5 mg corn starch
2.5 mg poly-N-vinylpyrrolidone 25
2.0 mg Aerosil®
0.5 mg

Magnesium stearate
225.0 mg total weight of the tablet, which is manufactured in the usual way on a tablet press

Example 2

50.0 mg of 4-hydroxy-4-androsten-3,17-dione
115.5 mg lactose
54.5 mg corn starch
2.5 mg poly-N-vinylpyrrolidone 25
2.0 mg Aerosil®
0.5 mg magnesium stearate
225.0 mg

Total weight of the tablet in the usual Made on a tablet press becomes  

Example 3

50.0 mg of 4-acetoxy-4-androsten-3,17-dione
115.5 mg lactose
54.5 mg corn starch
2.5 mg poly-N-vinylpyrrolidone 25
2.0 mg Aerosil®
0.5 mg magnesium stearate
225.0 mg

Total weight of the tablet in the usual Made on a tablet press becomes

Example 4 Composition of an oily solution

50.0 mg of 4-acetoxy-4-androsten-3,17-dione
378.4 mg castor oil
643.6 mg

Benzyl benzoate
1072.0 mg = 1 ml solution

The solution is filled into an ampoule and sterilized.

Claims (3)

1. Use of 4-hydroxy or 4- (C₂-C₁₂) acyloxy-4- androsten-3,17-dione (s) for the prophylaxis and therapy of Prostate hyperplasia. 2. Use of 4-hydroxy or 4- (C₂-C₁₂) acyloxy-4- androsten-3,17-dione (s) according to claim 1 in oral Pharmaceutical form. 3. Use of 4-hydroxy or 4- (C₂-C₁₂) acyloxy-4- androsten-3,17-dione (s) according to claim 1 in a for parenteral application suitable dosage form.