US3541209A - Method of alleviating hypertrophic conditions - Google Patents

Method of alleviating hypertrophic conditions Download PDF

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Publication number
US3541209A
US3541209A US675003A US3541209DA US3541209A US 3541209 A US3541209 A US 3541209A US 675003 A US675003 A US 675003A US 3541209D A US3541209D A US 3541209DA US 3541209 A US3541209 A US 3541209A
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United States
Prior art keywords
hydroxy
prostate
present
composition
progesterone
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Expired - Lifetime
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US675003A
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English (en)
Inventor
Friedmund Neumann
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Bayer Pharma AG
Original Assignee
Schering AG
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone

Definitions

  • This invention relates to a method for treating a patient suffering from hypertrophy of the prostate by intramuscular injection of 19-Nor-17a-hydroxy-progesterone ester.
  • the present invention relates to a method of alleviating certain hypertrophic conditions and to compositions therefor. More particularly, the present invention is concerned with the treatment of hypertrophic conditions of the prostate.
  • the essential active ingredient of the composition of the present invention is a 19-Nor-l7a-hydroxy-progesterone ester which, preferably, is administered by intramuscular injection in the form of an oily solution.
  • the present invention contemplates a method of treating a patient suffering from hypertrophy of the prostate, which comprises administering to the patient by intramuscular injection an effective amount of a composition having as the essential active ingredient a 19-Nor-17a-hydroxyprogesterone ester.
  • an injectable liquid composition for intramuscular injection in the treatment of hypertrophy of the prostate comprising a 19-Nor-17ot-hydroxy-progesterone ester and a pharmaceutical diluent.
  • the 19-Nor-l7a-hydroxy-progesterone ester will be the formiate, acetate, butyrate, caprylate, cyclopentylpropionate or caproate of 19-Nor-17a-hydroxyprogesterone.
  • the 19-Nor-17u-hydroxyprogesterone caproate will be the essential active ingredient of the composition which is applied by intramuscular injection in accordance with the present invention.
  • esters which are utilized according to the present invention do not have an estrogenic or androgenic side effect and only a slight antigonadotropic effect.
  • the preferred treatment will be the administration of 250 mg. between 2 and 3 times per week for the purpose of relieving pain, reduction of the size of prostate and improvement of urinary flow.
  • the administration of this medication should be continued as long as the condition of the patient requires.
  • composition which is to be administered in accordance with the present invention is formed by dissolving the 19-Nor-17a-hydroxy-progesterone ester in oils such as castor oil by the methods conventionally employed in galenic pharmacy. If desired, the solubility of the oily solutions can be improved by the introduction of diluents or agents which will improve the solubility, for instance benzyl benzoate.
  • a preferred composition according to the present invention is a solurecrystallization from isopropyl ether, has a melting point of between 123 and 124 C.
  • esters which are preferred according to the present invention may beproduced as.
  • EXAMPLE II 380 mg. of p-toluene sulfonic acid-1 H O are added to a suspension of 316 mg. of l7a-hydroxy-norprogesterone in 16 cc. of acetanhydride. The esterification is completed after 4 hours at 37 C. The excess of acetanhydride is decomposed with pyridine in ice water and the 3-enol-17-diester is extracted with ether. The ether extract is washed until neutral, dried over sodium sulfate and concentrated. The residue was dissolved in 35 cc. of methanol, reacted with 0.35 cc. of concentrated hydrochloric acid and heated under refluxing for 1 hour.
  • the methanolic solution is diluted with water and extracted with ether.
  • the ether extract is washed with water until neutral and dried over sodium sulfate and then concentrated.
  • the substance is recrystallized from isopropyl ether for purification. There is thus obtained a yield of 250 mg. of pure l7a-hydroxy-l9-norprogesterone-l7-acetate melting at 2l4216 C.
  • the yield amounts to 1.1 g. of pure 17a-hydroxy-19- norprogesterone-17-caproate having a melting point of 123-124 C.
  • EXAMPLE IV 0.66 g. of p-toluene sulfonic acid-1 H O are added to a suspension of 0.5 g. of 17a-hydr0xy-norprogesterone in 20 cc. of butyric acid anhydride under stirring and under a nitrogen atmosphere. After 4 hours at 37 C., 70 cc. of methanol and 0.7 cc. of concentrated hydrochloric acid are added to the clear solution and the same is cooked for 1 hour under refluxing and under a nitrogen atmosphere. The excess is extracted with ether, the ether extract is washed until neutral, dried over sodium sulfate and concentrated.
  • the thus obtained oil is dissolved in isopropyl ether, purified with activated carbon and the thus obtained colorless solution is again concentrated to dryness.
  • the obtained oily residue is found upon elemental analysis and upon tests under ultraviolet and infrared light to be pure '17a-hydroxy-19-norprogesterone-17-caprylate.
  • EXAMPLE VI 1 g. of 17a-hydroxy-19-norprogesterone is added to a mixture heated to a temperature of C. of 4 cc. of cyclopentylpropionic acid and 1 cc. of triiiuoroacetic acid anhydride. After 45 minutes of reaction at the same temperature the clear solution is added to water, the precipitated oil is taken up in ether, the ether extract is first washed with a saturated sodium carbonate solution and subsequently with water until neutral. It is then dried over sodium sulfate and concentrated. The obtained crude oil is dissolved in isopropyl ether, purified with activated carbon, and the now obtained colorless solution is concentrated to dryness. A colorless oily residue can definitely be identified as 17a-hydroxy-19-n0rprogesterone-l7-cyclopentylpropionate.
  • the injectable liquid composition of the present invention may be prepared for instance of 25 mg. of 19-Nor- 17a-hydroxy-progesterone caproate by dissolving the same in 0.6 ml. of castor oil and 0.4 ml. of benzylbenzoate, or by dissolving the above caproate or other ester of 19-Norl7a-hydroxy-progesterone in 1.0 ml. of sesame oil.
  • a method of treating a patient suffering from hypertrophy of the prostate which comprises administering to said patient by intramuscular injection an effective amount of a composition including as the essential active ingredient a compound selected from the group consisting of the formate, acetate, butyrate, caprylate, cyclopentylpropionate and caproate of 19-Nor-17alpha-hydroxy progesterone.
  • said effective amount of said composition is such as to contain between about 50 and 1000 mg. of said 19-Nor-17alphahydroxy-progesterone ester.
  • a method as defined in claim 1, wherein said effective amount of said composition is such as to contain about 250 mg. of said 19-Nor-17alpha-hydroxy-progesterone ester.
  • said effec tive amount of said composition is such as to contain about 250 mg. of 19-Nor-17alpha-hydroxy-progesterone caproate; and wherein intramuscular injection of said composition is carried out between 2 and 3 times per week.
  • said effective amount of said composition is such as to contain 6 References Cited FOREIGN PATENTS 9/1961 Great Britain. 2/ 1960 Germany.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US675003A 1965-03-24 1967-10-12 Method of alleviating hypertrophic conditions Expired - Lifetime US3541209A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DESC036759 1965-03-24

Publications (1)

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US3541209A true US3541209A (en) 1970-11-17

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US675003A Expired - Lifetime US3541209A (en) 1965-03-24 1967-10-12 Method of alleviating hypertrophic conditions

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US (1) US3541209A (enrdf_load_stackoverflow)
BE (1) BE678366A (enrdf_load_stackoverflow)
FR (1) FR5425M (enrdf_load_stackoverflow)
GB (1) GB1126892A (enrdf_load_stackoverflow)
NL (1) NL151903B (enrdf_load_stackoverflow)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6774122B2 (en) 2000-01-10 2004-08-10 Astrazeneca Ab Formulation
US10709716B2 (en) 2011-07-28 2020-07-14 Lipocine Inc. 17-hydroxyprogesterone ester-containing oral compositions and related methods
US11590147B2 (en) 2015-06-22 2023-02-28 Lipocine Inc. 17-hydroxyprogesterone ester-containing oral compositions and related methods

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9827727D0 (en) 1998-12-16 1999-02-10 Pfizer Ltd Antiparasitic formulations

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1074582B (de) * 1960-02-04 Schering Aktiengesellschaft, Ber Im Verfahren zur Herstellung progesteronartig wirksamer Steroide mit bisher unerreichter Hohe der Wirksamkeit
GB876902A (en) * 1957-03-09 1961-09-06 Syntex Sa New cyclopentanophenanthrene derivatives and process for the production thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1074582B (de) * 1960-02-04 Schering Aktiengesellschaft, Ber Im Verfahren zur Herstellung progesteronartig wirksamer Steroide mit bisher unerreichter Hohe der Wirksamkeit
GB876902A (en) * 1957-03-09 1961-09-06 Syntex Sa New cyclopentanophenanthrene derivatives and process for the production thereof

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6774122B2 (en) 2000-01-10 2004-08-10 Astrazeneca Ab Formulation
US20050043285A1 (en) * 2000-01-10 2005-02-24 Astrazeneca Ab Formulation
US7456160B2 (en) 2000-01-10 2008-11-25 Astrazeneca Ab Formulation
US8329680B2 (en) 2000-01-10 2012-12-11 Astrazeneca Ab Formulation
US8466139B2 (en) 2000-01-10 2013-06-18 Astrazeneca Ab Formulation
US10709716B2 (en) 2011-07-28 2020-07-14 Lipocine Inc. 17-hydroxyprogesterone ester-containing oral compositions and related methods
US11471470B2 (en) 2011-07-28 2022-10-18 Lipocine Inc. 17-hydroxyprogesterone ester-containing oral compositions and related methods
US11590147B2 (en) 2015-06-22 2023-02-28 Lipocine Inc. 17-hydroxyprogesterone ester-containing oral compositions and related methods

Also Published As

Publication number Publication date
BE678366A (enrdf_load_stackoverflow) 1966-09-26
NL151903B (nl) 1977-01-17
GB1126892A (en) 1968-09-11
FR5425M (enrdf_load_stackoverflow) 1967-10-02
NL6603833A (enrdf_load_stackoverflow) 1966-09-26

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