DE2345376A1 - PHARMACEUTICAL PREPARATION II - Google Patents
PHARMACEUTICAL PREPARATION IIInfo
- Publication number
- DE2345376A1 DE2345376A1 DE19732345376 DE2345376A DE2345376A1 DE 2345376 A1 DE2345376 A1 DE 2345376A1 DE 19732345376 DE19732345376 DE 19732345376 DE 2345376 A DE2345376 A DE 2345376A DE 2345376 A1 DE2345376 A1 DE 2345376A1
- Authority
- DE
- Germany
- Prior art keywords
- mesterolone
- esters
- scheringag
- effect
- dab
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- OFQCQIGMURIECL-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]-2',6'-dimethylspiro[isoquinoline-4,4'-oxane]-1,3-dione;phosphoric acid Chemical compound OP(O)(O)=O.O=C1N(CCN(CC)CC)C(=O)C2=CC=CC=C2C21CC(C)OC(C)C2 OFQCQIGMURIECL-UHFFFAOYSA-N 0.000 title description 2
- 239000000825 pharmaceutical preparation Substances 0.000 title description 2
- 229960005272 mesterolone Drugs 0.000 claims description 22
- UXYRZJKIQKRJCF-TZPFWLJSSA-N mesterolone Chemical compound C1C[C@@H]2[C@@]3(C)[C@@H](C)CC(=O)C[C@@H]3CC[C@H]2[C@@H]2CC[C@H](O)[C@]21C UXYRZJKIQKRJCF-TZPFWLJSSA-N 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 12
- 230000001430 anti-depressive effect Effects 0.000 claims description 5
- 239000000935 antidepressant agent Substances 0.000 claims description 5
- 229940005513 antidepressants Drugs 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 230000036651 mood Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 3
- 238000012937 correction Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000019634 flavors Nutrition 0.000 claims description 2
- NOQGZXFMHARMLW-UHFFFAOYSA-N Daminozide Chemical compound CN(C)NC(=O)CCC(O)=O NOQGZXFMHARMLW-UHFFFAOYSA-N 0.000 claims 1
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 6
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 150000003431 steroids Chemical class 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 208000020401 Depressive disease Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229960002903 benzyl benzoate Drugs 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 229960003604 testosterone Drugs 0.000 description 3
- 206010002261 Androgen deficiency Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 229940030486 androgens Drugs 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 231100000507 endocrine disrupting Toxicity 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 2
- 208000015238 neurotic disease Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- GCKMFJBGXUYNAG-UHFFFAOYSA-N 17alpha-methyltestosterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C)(O)C1(C)CC2 GCKMFJBGXUYNAG-UHFFFAOYSA-N 0.000 description 1
- NOIIUHRQUVNIDD-UHFFFAOYSA-N 3-[[oxo(pyridin-4-yl)methyl]hydrazo]-N-(phenylmethyl)propanamide Chemical compound C=1C=CC=CC=1CNC(=O)CCNNC(=O)C1=CC=NC=C1 NOIIUHRQUVNIDD-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 206010011971 Decreased interest Diseases 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 206010013496 Disturbance in attention Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 206010024870 Loss of libido Diseases 0.000 description 1
- GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 description 1
- DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 206010043298 Testicular atrophy Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-N Tyramine Natural products NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000012826 adjustment disease Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 201000010788 atrophy of testis Diseases 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229950004783 cipionate Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 238000000537 electroencephalography Methods 0.000 description 1
- 201000003104 endogenous depression Diseases 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960001566 methyltestosterone Drugs 0.000 description 1
- 208000025319 neurotic depression Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960003057 nialamide Drugs 0.000 description 1
- 229960001779 pargyline Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 230000003304 psychophysiological effect Effects 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100001044 testicular atrophy Toxicity 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229960003732 tyramine Drugs 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-O tyraminium Chemical compound [NH3+]CCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-O 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
Description
SCHERiNGAGSCHERiNGAG
2345 3 76 Berlin, den 6. September 19732345 3 76 Berlin, September 6, 1973
Die Erfindung "betrifft Arzneimittel auf Basis von Mesterolon und dessen 17-Estern, die neuropsychotrope Wirkungen haben. Diese neuen Arzneimittel zeichnen sich "insbesondere durch antidepressive, stimmungs- und leistungsverbessernde Eigenschaften aus.The invention "relates to medicaments based on mesterolone and its 17-esters, which have neuropsychotropic effects. These new drugs are characterized "in particular by antidepressant, mood and performance-improving properties the end.
Mesterolon (la-Methyl-5a-androstan-17ß-ol-3-on) und seine Ester sind beispielsweise aus der DT PS 1 152 100 bekannt.Mesterolone (la-methyl-5a-androstan-17ß-ol-3-one) and his Esters are known from DT PS 1,152,100, for example.
Es ist bekannt, daß einige Steroide eine dämpfende Wirkung auf das Zentralnervensystem ausüben und hypnotische bzw. anästhetische Wirkungen besitzen. Diese Steroide haben jedoch keine Bedeutung als Arzneimittel in den erfindungsgemäßen Indikationen, da sie z.B. zu einer starken Depression des Zentralnervensystems führen.It is known that some steroids have a depressant effect on the central nervous system and are hypnotic or anesthetic Have effects. However, these steroids have no meaning as drugs in the indications according to the invention, as they lead, for example, to severe central nervous system depression.
Des weiteren ist bekannt, daß bei Mangel an körpereigenen Sexualhormonen mit Steroidstruktur, z.B. Androgenmangel, auch die mit dem Defizit verbundenen psychischen Störungen durch Substitution mit endokrinaktiven Steroiden behoben werden können.It is also known that if there is a lack of endogenous sex hormones with steroid structure, e.g. androgen deficiency, also those with the deficit-related mental disorders can be corrected by substitution with endocrine disrupting steroids.
S09812/1Q67S09812 / 1Q67
SCHERINGAGSCHERINGAG
— 2 — Patentabteilung- 2 - Patent Department
Für Testosteron wurde weiterhin beschrieben, daß es bei Infusion an Gesunden einen Leistungsabfall in bestimmten psychologischen Testverfahren verzögerte (W. Vogel et al. , Electroenceph. elin. Neurophysiol. 1971 4-00). Auch diese Wirkungen haben jedoch für die erfindungsgemäße Anwendung keine Bedeutung, da Testosteron diese Wirkung nur bei Applikation als alkoholische Infusion zeigt. Hinzu kommt, daß Testosteron infolge seiner gonadotropin-hemmenden Wirkung zur Hodenatrophie und Abfall der körpereigenen Androgene führt. Androgene mit besserer oraler Wirksamkeit wie Methyltestosteron können darüberhinaus noch zu schweren Leberschädigungen führen.Testosterone has also been described as delaying a decrease in performance in certain psychological test methods when infused into healthy persons (W. Vogel et al., Electroenceph. Elin. Neurophysiol. 1971 4-00). However, these effects are also of no importance for the application according to the invention, since testosterone only shows this effect when administered as an alcoholic infusion. In addition, as a result of its gonadotropin-inhibiting effect, testosterone leads to testicular atrophy and a decrease in the body's own androgens. Androgens with better oral efficacy such as methyltestosterone can also lead to severe liver damage.
Als wirkende Bestandteile in Psychopharmaka mit antidepressiver Wirkung sind bekannt die sogenannten tricyclischen Antidepressiva wie Amitriptylin, Imipramin und Desipramin, und Monoamino-oxydase-Hemmer, wie Nialamid und Pargylin, sowie Stimulantia vom Amphetamin-Typ. Diesen Wirkstoffen ist gemeinsam, daß sie eine hohe Toxizität besitzen. Weiterhin haben sie den Nachteil, daß die antidepressive Wirkung erstThe so-called tricyclic drugs are known as active ingredients in psychotropic drugs with an antidepressant effect Antidepressants such as amitriptyline, imipramine, and desipramine, and monoamine oxidase inhibitors, such as nialamide and pargyline, and amphetamine-type stimulants. What these active substances have in common is that they have a high toxicity. Farther they have the disadvantage that the antidepressant effect only
- 3 -509812/1067- 3 -509812/1067
SCHERINGAGSCHERINGAG
— 3 — Patentabteilung- 3 - Patent Department
nach Wochen eintritt. Diese Nachteile stellen insbesondere bei suicidgefährdeten Personen ein hohes Risiko dar. Des weiteren haben diese Wirkstoffe eine Reihe von Nebenwirkungen. Besonders unerwünschte Nebenwirkungen der tricyclischen Antidepressiva sind neurologische und vegetative Symptome, wie z.B. Sehstörungen, Herzrythmusstörungen, Mundtrockenheit, Bewußtseinsveränderungen, sowie in manchen Fällen auch gefährliche Veränderungen des Blutbildes. Unerwünschte Nebenwirkungen der Monoaminooxydase-Hemmer sind vor allem Leberschaden und gefährliche 'Hypertoniekrisen bei Genuß von tyraminhaltigen Lebensmitteln. Bei Amphetaminen hat die starke zentralstimulierende und abhängigkeitsbildende Wirkung dieser Substanzen dazu geführt, daß sie praktisch heute nicht mehr als Antidepressiva verwendet werden.occurs after weeks. These disadvantages represent a high risk in particular for people at risk of suicide. Furthermore these active ingredients have a number of side effects. Particularly undesirable side effects of the tricyclic antidepressants are neurological and vegetative symptoms, such as visual disturbances, cardiac arrhythmias, dry mouth, changes in consciousness, and in some cases dangerous changes in the blood count. Undesirable side effects of monoamine oxidase inhibitors are primarily liver damage and dangerous hypertension crises when eating foods containing tyramine. In amphetamines, the strong central stimulant and dependency-building Effect of these substances led to the fact that they are practically no longer used as antidepressants today.
Es wurde nun gefunden, daß Mesterolon und seine Ester eine ausgesprochen antidepressive Wirkung zeigen. Dieses Ergebnis ist zum ersten Mal bei einer Substanz mit Steroidstruktur erhalten worden.It has now been found that mesterolone and its esters are pronounced one show antidepressant effects. This result has been obtained for the first time with a substance with a steroid structure been.
Mesterolon und seine Ester wurden im placebo-kontrollierten Doppelblindversuch durch quantitative Pharmaco-Elektroencephalographie (CEEG) undMesterolone and its esters were tested in a placebo-controlled double-blind experiment by quantitative pharmaco-electroencephalography (CEEG) and
509812/1067509812/1067
SCHERINGAGSCHERINGAG
— 4 — Patentabteilung- 4 - Patent Department
durch, die Methode der evozierten Potentiale (T.M. Itil et al., Nervenarzt 44 (1973) 65) an Menschen untersucht. Weiterhin wurden die Wirkungen und Nebenwirkungen durch verschiedene Hating Scales, z.B. für neurologische und psychosomatische Symptomatik, durch· Self-Rating Scales für Sedierung, Angst und Depression, sowie durch ärztliche Interviews erfaßt.by using the evoked potentials method (T.M. Itil et al., Nervenarzt 44 (1973) 65) examined on humans. Farther the effects and side effects were due to different Hating scales, e.g. for neurological and psychosomatic Symptoms through · Self-Rating Scales for Sedation, Anxiety and depression, as well as through medical interviews.
Bei der praktischen Anwendung von Mesterolon und dessen Estern tritt die gewünschte Wirkung bereits kurz nach Applikation, nach etwa 2-3 Stunden, ein. Dies ist überraschend, da von endokrinwirksamen Steroiden allgemein bekannt ist, daß die Wirkung erst nach längerer Behandlungsdauer eintritt. Im Fall von Mesterolon in seinen bekannten Anwendungen ist an sich bekannt, daß die Wirkung erst nach Wochen der Behandlung einsetzt.In the practical application of mesterolone and its esters the desired effect occurs shortly after application, after about 2-3 hours. This is surprising since endocrine disrupting steroids are generally known to be effective only occurs after a long period of treatment. In the case of mesterolone in its known uses, it is known per se that the effect only sets in after weeks of treatment.
Der'Vorteil von Arzneimitteln auf der Basis von Mesterolon und dessen Estern liegt insbesondere darin, daß selbst bei oralen Einzeldosen in der Größenordnung von 2 g keine neurologischen, vegetativen oder sonstigen Nebenwirkungen hervorgerufen werden. Eine Überdosierung würde also nicht letzten Endes zum Tode führen. The ' advantage of medicaments based on mesterolone and its esters lies in the fact that even with single oral doses of the order of 2 g no neurological, vegetative or other side effects are caused. Overdosing would not ultimately lead to death.
- 5 509812/1067 - 5 509812/1067
SCHERINGAGSCHERINGAG
— 5 —- 5 - PatentabteilungPatent department
Des weiteren ist es auch von Vorteil, daß auch bei langandauernder Anwendung von Mesterolon und dessen Estern keine Abhängigkeit, wie sie bei bekannten Antidepressiva möglich ist, entsteht.Furthermore, it is also advantageous that even with long-term Use of mesterolone and its esters no dependence, as is possible with known antidepressants is, arises.
Des weiteren betrifft die Erfindung eine Methode zur Behandlung von Depressionen und Störungen von.Stimmung, Verhalten und Leistungsfähigkeit mit den erfindungsgemäßen Arzneimitteln. Hierzu gehören insbesondere endogene, neurotische und reaktive Depressionen, Altersdepressionen, Klimakteriums- und Involutionsdepressionen sowie/den klimakterischen Depressionen verwandte Zustände mit Veränderungen und Störungen im affektiven Bereich, nachlassende Leistung und Konzentration und vermehrte Reizbarkeit, mit und ohne Mangel körpereigener Hormone.The invention also relates to a method for treating depression and disorders of mood, behavior and Performance with the medicaments according to the invention. These include, in particular, endogenous, neurotic and reactive Depression, age depression, climacteric and involutional depression as well as / related to climacteric depression States with changes and disorders in the affective area, Decreasing performance and concentration and increased irritability, with and without a lack of endogenous hormones.
Darüberhinaus sind die erfindungsgemäßen Arzneimittel auch zur Behandlung von Konzentrations- und Gedächtnisschwäche, auch bei Personen ohne Androgenmangel, sowie von psychophysiologischen Erkrankungen, wie Nachlassen der allgemeinen Leistungsfähigkeit, Müdigkeit, Interessenverlust, und bei Schlafstörungen, wie Schlaftverlust in der Nacht bei Müdigkeit am Tage, bei Störungen der Sexualität, wie Libido- und Potenzverlust bei jüngeren Patienten ohne Steroidhormonmangel, geeignet.In addition, the medicaments according to the invention are also used for the treatment of poor concentration and memory problems, also in people without androgen deficiency, as well as psychophysiological Illnesses such as a decline in general performance, fatigue, loss of interest, and with Sleep disorders, such as loss of sleep at night when you are tired during the day, for disorders of sexuality, such as loss of libido and potency in younger patients without steroid hormone deficiency.
- 6 509812/1067 - 6 509812/1067
SCHERINGAGSCHERINGAG
— 6 — Patentabteilung- 6 - Patent Department
In der medizinischen Praxis können die erfindungsgemäßen Arzneimittel auf Basis von Mesterolon und dessen Estern subcutan, intramuskulär oder per os appliziert werden. Die tägliche Dosis beträgt 0,1 - 1000 mg, vorzugsweise 1 - 100 mg. Die Dosis kann einmalig oder in mehreren Gaben verabfolgt werden.The medicaments according to the invention can be used in medical practice based on mesterolone and its esters subcutaneously, administered intramuscularly or per os. The daily dose is 0.1-1000 mg, preferably 1-100 mg. The dose can be administered once or in several doses.
Die Formulierung der erfindungsgemäßen Arzneimittel auf Basis von Mesterolon und dessen Estern erfolgt in an sich bekannter Weise, in dem das Mesterolon und dessen Ester, insbesondere solche Ester mit 1-8 Kohlenstoffatomen, mit den in der galenischen Pharmazie gebräuchlichen Trägersubstanzen, Verdünnungsmitteln, Geschmackskorrigentien usw. verarbeitet und in der gewünschten Applikationsform überführt werden, wie z.B. Tabletten, Dragees, Kapseln, Lösungen usw. Für Injektionen kommen insbesondere ölige Lösungen, wie z.B. Lösungen in Sesam-, Rizinus- und Baumwollsamenöl infrage.. Gewünschtenfalls können zur Steigerung der Löslichkeit noch Verdünnungsmittel oder Lösungsvermittler, wie z.B. Benzylbenzoat oder Benzylalkohol zugesetzt werden. Zur Erreichung einer protrahierten Wirkung können Mesterolon und dessen Ester auch in mikroverkapselter Form eingesetzt werden. Für die orale Applikation sind insbesondereThe formulation of the medicaments according to the invention based on mesterolone and its esters takes place in a manner known per se Way in which the mesterolone and its esters, especially those esters with 1-8 carbon atoms, with those in the galenic Carriers commonly used in pharmacy, diluents, flavor corrections, etc. processed and in the desired form Application form are transferred, such as tablets, dragees, capsules, solutions, etc. For injections come in particular Oily solutions, such as solutions in sesame, castor and cottonseed oil, can be used thinners or solubilizers, such as benzyl benzoate or benzyl alcohol, are added to the solubility will. To achieve a protracted effect, mesterolone and its esters can also be used in microencapsulated form can be used. For oral application are in particular
- 7 -509812/1Q87- 7 -509812 / 1Q87
SCHERINGAGSCHERINGAG
- 7 ~ Patentabteilung- 7 ~ Patent Department
Tabletten, Kapseln, Dragees, Pillen, Suspensionen und Lösungen geeignet.Tablets, capsules, coated tablets, pills, suspensions and solutions are suitable.
Die erfindungsgemäße Wirkung des Mesterolons und seiner Ester tritt nicht nur bei Injektion, sondern auch bei oraler Applikation gleichermaßen auf. Die Wirkstoffmenge in den so formulierten Arzneimitteln beträgt 0,1 - 200 mg, vorzugsweise 1-50 mg.The inventive effect of mesterolone and its esters occurs not only with injection but also with oral administration. The amount of active ingredient in the so formulated Drugs is 0.1-200 mg, preferably 1-50 mg.
Nachstehend wird die Formulierung einiger Arzneimittelspezialitäten anhand verschiedener Ausführungsbeispiele näher erläutert:Below is the formulation of some drug specialties explained in more detail on the basis of various exemplary embodiments:
- 8 509812/1067 - 8 509812/1067
SCHERINGAGSCHERINGAG
_ 8 — Patentabteilung_ 8 - Patent Department
10,0 mg 17ß-Hydroxy-la-methyl-5a-androstan-3-on (Mesterolon) mit einer spezifischen äußeren Oberfläche von 20 cm /g und einem mittleren Teilchendurchmesser von 7 /um werden mit10.0 mg 17ß-hydroxy-la-methyl-5a-androstan-3-one (mesterolone) with a specific outer surface area of 20 cm / g and an average particle diameter of 7 / um will be with
36,0 mg Milchzucker (DAB 6; USPXVII),36.0 mg milk sugar (DAB 6; USPXVII),
66,565 mg Maisstärke (USP XVII), 1,4 mg Gelatine (DAB 6; USP XVII), 0,024 mg p-Oxybenzoesäuremethylester (DAB 6, USP XVII), 0,011 mg p-Oxybenzoesäurepropylester (DAB 6, USP XVII), 4,8 mg Talkum (DAB 6, USP XVII) und66.565 mg corn starch (USP XVII), 1.4 mg gelatin (DAB 6; USP XVII), 0.024 mg p-oxybenzoic acid methyl ester (DAB 6, USP XVII), 0.011 mg propyl p-oxybenzoate (DAB 6, USP XVII), 4.8 mg talc (DAB 6, USP XVII) and
1,2 mg Magnesiumstearat (USP XVII)1.2 mg magnesium stearate (USP XVII)
homogen gemischt und ohne vorherige Granulierung zu Tabletten mit Bruchkerbe von 120 mg Gewicht mit einem Durchmesser von etwa 7 mm bei einer Höhe von 2,7 bis 2,9 mm gepreßt.homogeneously mixed and pressed without prior granulation to give tablets with a breaking notch weighing 120 mg with a diameter of about 7 mm and a height of 2.7 to 2.9 mm.
25 ,0 mg Mesterolon werden mit 60,5 mg Lactose (DAB 7, USP XVII), 32,165 mg Maisstärke (DAB 7, USP XVII), 2,0 mg Poly-N-vinylpyrrolidon 25, 25.0 mg mesterolone are mixed with 60.5 mg lactose (DAB 7, USP XVII), 32.165 mg corn starch (DAB 7, USP XVII), 2.0 mg poly-N-vinylpyrrolidone 25,
509812/1067509812/1067
ORJGlNAL INSPECTEDORJGlNAL INSPECTED
- 9 - Patentabteilung- 9 - Patent Department
0,024 mg p-Hydroxybenzoesäuremethylester (DAB 7, USP XVII), 0,011 mg p-Hydroxybenzoesäurepropylester (DAB 7» USP XVII) und 0,3 mg Magnesiumstearat (USP XVII)0.024 mg p-hydroxybenzoic acid methyl ester (DAB 7, USP XVII), 0.011 mg propyl p-hydroxybenzoate (DAB 7 »USP XVII) and 0.3 mg magnesium stearate (USP XVII)
analog Beispiel 1 zu Tabletten von 120 mg Endgewicht gepreßt.Compressed analogously to Example 1 to give tablets of 120 mg final weight.
Zur Herstellung einer Injektionslösung werden 20,0 mg Mesterolon inTo prepare a solution for injection, 20.0 mg of mesterolone in
618,6 mg Benzylbenzoat (USP XVII) und 353,^ mg Rizinusöl (DAB 7, USP XVII) gelöst, die Lösung steril filtriert und unter aseptischen Bedingungen in 1 ml-Ampullen abgefüllt.618.6 mg benzyl benzoate (USP XVII) and 353.1 mg castor oil (DAB 7, USP XVII) dissolved the The solution is sterile filtered and filled into 1 ml ampoules under aseptic conditions.
Analog Beispiel 3 werdenAnalogous to example 3
25,0 mg ^ß-Cyclopentylprbpionylo^-la-methyl-^a-androstan-25.0 mg ^ ß-Cyclopentylprbpionylo ^ -la-methyl- ^ a-androstan-
3-on (Mesterolon-cipionat) in 152,3 mg Benzylbenzoat und3-one (mesterolone cipionate) in 152.3 mg benzyl benzoate and
86,4 mg Rizinusöl gelöst und als 1 ml-Ampullen abgefüllt.86.4 mg of castor oil dissolved and filled as 1 ml ampoules.
- 10 -- 10 -
ORIGINAL INSPECTEDORIGINAL INSPECTED
509812/1067509812/1067
— 10 — Patentabteilung- 10 - Patent Department
SCHERINGAGSCHERINGAG
bteilungdivision
Je 0,5 mg Mesterolon (mikronisiert mit einer Teilchengröße von 2-8 /um) werden mit 150 mg Milchzucker (USP XVII) homogen gemischt und in Hartgelatine-Steckkapseln (5 x 15 nun) abgefüllt.0.5 mg each of mesterolone (micronized with a particle size from 2-8 / µm) become homogeneous with 150 mg milk sugar (USP XVII) mixed and filled into hard gelatine capsules (5 x 15 well).
- 11 -- 11 -
509812/106 7509812/106 7
Claims (5)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732345376 DE2345376A1 (en) | 1973-09-06 | 1973-09-06 | PHARMACEUTICAL PREPARATION II |
| GB39140/74A GB1483650A (en) | 1973-09-06 | 1974-09-06 | Pharmaceutical preparations based on mesterolone |
| US503732A US3908007A (en) | 1973-09-06 | 1974-09-06 | Treatment of mental depression |
| NL7411859A NL7411859A (en) | 1973-09-06 | 1974-09-06 | METHOD FOR PREPARING A MEDICINAL PRODUCT. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732345376 DE2345376A1 (en) | 1973-09-06 | 1973-09-06 | PHARMACEUTICAL PREPARATION II |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2345376A1 true DE2345376A1 (en) | 1975-03-20 |
Family
ID=5892030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19732345376 Withdrawn DE2345376A1 (en) | 1973-09-06 | 1973-09-06 | PHARMACEUTICAL PREPARATION II |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US3908007A (en) |
| DE (1) | DE2345376A1 (en) |
| GB (1) | GB1483650A (en) |
| NL (1) | NL7411859A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993024128A1 (en) * | 1992-06-03 | 1993-12-09 | Mattern Et Partner Pharmazeutische Entwicklungs- Und Handelsges. Mbh | Androgens for stimulating the central nervous system and for treating osteoporosis |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4415591A (en) * | 1981-06-04 | 1983-11-15 | Georgia Tech Research Institute | Use of aminoalkyl phenyl sulfide derivatives for the treatment of hypertension |
| US5883087A (en) * | 1991-01-07 | 1999-03-16 | Pherin Corporation | Androstane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods |
| ATE255898T1 (en) * | 1993-06-15 | 2003-12-15 | Pherin Corp | ANDROSTAN STEROIDS AS NEUROCHEMICAL INITIATORS OF A CHANGE IN HYPOTHALAMUS FUNCTION IN HUMAN AND RELATED PHARMACEUTICAL PREPARATIONS AND METHODS |
| CN1057531C (en) * | 1993-06-15 | 2000-10-18 | 弗林公司 | Androstane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical |
| WO2009049030A1 (en) * | 2007-10-09 | 2009-04-16 | Triton Biopharma, Llc | Method to use compositions having antidepressant anxiolytic and other neurological activity and compositions of matter |
| BE1027858B1 (en) * | 2019-12-13 | 2021-07-14 | Georges Debled | Pharmaceutical composition for contraception in women |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1152100B (en) * | 1960-12-23 | 1963-08-01 | Schering Ag | Process for the preparation of 1ª ‡ -Methyl-3-ketosteroids |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1122944B (en) * | 1960-04-06 | 1962-02-01 | Schering Ag | Process for the preparation of 1ª ‡ -Methyl-3-ketosteroids |
-
1973
- 1973-09-06 DE DE19732345376 patent/DE2345376A1/en not_active Withdrawn
-
1974
- 1974-09-06 GB GB39140/74A patent/GB1483650A/en not_active Expired
- 1974-09-06 US US503732A patent/US3908007A/en not_active Expired - Lifetime
- 1974-09-06 NL NL7411859A patent/NL7411859A/en not_active Application Discontinuation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1152100B (en) * | 1960-12-23 | 1963-08-01 | Schering Ag | Process for the preparation of 1ª ‡ -Methyl-3-ketosteroids |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993024128A1 (en) * | 1992-06-03 | 1993-12-09 | Mattern Et Partner Pharmazeutische Entwicklungs- Und Handelsges. Mbh | Androgens for stimulating the central nervous system and for treating osteoporosis |
Also Published As
| Publication number | Publication date |
|---|---|
| US3908007A (en) | 1975-09-23 |
| GB1483650A (en) | 1977-08-24 |
| NL7411859A (en) | 1975-03-10 |
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