DE948184C - Process for the production of aqueous solutions of steroid hormones - Google Patents
Process for the production of aqueous solutions of steroid hormonesInfo
- Publication number
- DE948184C DE948184C DEF10970A DEF0010970A DE948184C DE 948184 C DE948184 C DE 948184C DE F10970 A DEF10970 A DE F10970A DE F0010970 A DEF0010970 A DE F0010970A DE 948184 C DE948184 C DE 948184C
- Authority
- DE
- Germany
- Prior art keywords
- water
- dimethyl
- phenylpyrazolone
- sodium salicylate
- phenyl
- 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.)
- Expired
Links
- 239000003270 steroid hormone Substances 0.000 title claims description 10
- 239000007864 aqueous solution Substances 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 11
- 150000007513 acids Chemical class 0.000 claims description 9
- 159000000000 sodium salts Chemical class 0.000 claims description 7
- VNOYHZYNOWVUFB-UHFFFAOYSA-N 4-benzylpyrazol-3-one Chemical class O=C1N=NC=C1CC1=CC=CC=C1 VNOYHZYNOWVUFB-UHFFFAOYSA-N 0.000 claims description 3
- QELUYTUMUWHWMC-UHFFFAOYSA-N Edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 claims 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 22
- 229960004025 sodium salicylate Drugs 0.000 description 22
- 239000000243 solution Substances 0.000 description 14
- RJKFOVLPORLFTN-STHVQZNPSA-N Progesterone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC(=O)CC4)CC3)CC2)CC1 RJKFOVLPORLFTN-STHVQZNPSA-N 0.000 description 11
- RJKFOVLPORLFTN-LEKSSAKUSA-N Syngestrets Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 11
- 239000000186 progesterone Substances 0.000 description 11
- 229960003387 progesterone Drugs 0.000 description 11
- ITRJWOMZKQRYTA-RFZYENFJSA-N Cortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O ITRJWOMZKQRYTA-RFZYENFJSA-N 0.000 description 8
- 229960003290 cortisone acetate Drugs 0.000 description 8
- 239000007924 injection Substances 0.000 description 5
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 5
- VPGRYOFKCNULNK-ACXQXYJUSA-N Deoxycorticosterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 VPGRYOFKCNULNK-ACXQXYJUSA-N 0.000 description 4
- 229960004486 Desoxycorticosterone acetate Drugs 0.000 description 4
- 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 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 229940051880 analgesics and antipyretics Pyrazolones Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drugs Drugs 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 229960003604 Testosterone Drugs 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- 231100000486 side effect Toxicity 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 150000003673 urethanes Chemical class 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N Gentisic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 Hormone Drugs 0.000 description 1
- 210000002966 Serum Anatomy 0.000 description 1
- 229950004644 Sodium Gentisate Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 229940083761 high-ceiling diuretics Pyrazolone derivatives Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000000147 hypnotic Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- MOIJZWWOFOQFMH-UHFFFAOYSA-M sodium;2,5-dihydroxybenzoate Chemical compound [Na+].OC1=CC=C(O)C(C([O-])=O)=C1 MOIJZWWOFOQFMH-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
Description
Verfahren zur Herstellung wäßriger Lösungen von Steroidhormonen Es ist bereits bekannt, wäßrige Progesteron-Lösungen dadurch herzustellen, daß man Urethane als Lösungsvermittler verwendet. Um jedoch für Injektionszwecke geeignete Mengen von Progesteron in Lösung zu bringen, muß man sa beträchtliche Mengen Urethan verwenden, daß unerwünschte Nebenwirkungen auftreten. Es ist weiterhin bekannt, leicht wasserlösliche Pyrazolone als Lösungsvermittler für schwerlösliche Arzneimittel zu verwenden. Ferner ist die Verwendung von Salzen der Oxybenzoesäuren als Lösungsvermittler bekannt. Es sind jedoch verhältnismäßig hohe Konzentrationen dieser Lösungsvermittler erforderlich, um schwerlösliche Arzneimittel in Lösung zu bringen, so daß im Falle von Injektionen Reizwirkungen auf treten können.Process for the preparation of aqueous solutions of steroid hormones Es is already known to produce aqueous progesterone solutions that one Urethanes used as solubilizers. However, to be suitable for injections Bringing amounts of progesterone into solution requires a considerable amount of urethane use that undesirable side effects occur. It is also known Easily water-soluble pyrazolones as solubilizers for poorly soluble drugs to use. Furthermore, the use of salts of oxybenzoic acids as solubilizers known. However, there are relatively high concentrations of these solubilizers required to bring poorly soluble drugs into solution, so that in the event Injections may cause irritation.
Es wurde nun gefunden, daß man für Injektionen geeignete wäßrige Lösungen von Steroidhormonen erhalten kann, wenn man Natriumsalze von Oxybenzoe,säuren zusammen mit in Wasser leicht lösliehen Phenylmethylpyrazolonen als Lösungsvermittler verwendet. Dabei zeigt sich, daß man mit geringen Konzentrationen von Phenylmethyipyrazolonen, die zum Auflösen eines Steroidhormons nicht ausreichen, stabile Lösungen' erzielen kann, wenn man kleine Mengen.-von Natriumsalzen von Oxybenzoesäu.ren zugibt.It has now been found that aqueous solutions suitable for injections can be obtained of steroid hormones can be obtained by taking sodium salts of oxybenzoic acids together with easily soluble in water Phenylmethylpyrazolones as solubilizers used. It turns out that with low concentrations of Phenylmethyipyrazolonen, which are insufficient to dissolve a steroid hormone, result in 'stable solutions' if small amounts of sodium salts of oxybenzoic acids are added.
Auf diese Weise gelingt es, Lösungen herzustellen, welche bei einem Gehalt von insgesamt etwa 30 bis 50 0/a .an Lösungsvermittlern für Injektionen geeignete Mengen von Steroidhormonen erhalten. Gegenüber den bekannten, unter Verwendung von Urethanen als Lösungsvermittler hergestellten Lösungen zeichnen sich die gemäß dem Verfahren der vorliegenden Erfindung gewonnenen Lösungen dadurch aus, daß sie keinerlei hypnotische Nebenwirkungen aufweisen. Außerdem werden die Wirkungen der Hormone, z. B. bei Cortison, durch die LösungsvermittleT günstig beeinflußt.In this way, it is possible to produce solutions that are useful for a Total content of about 30 to 50% of solubilizers suitable for injections Received amounts of steroid hormones. Compared to the known, using Urethanes prepared as solubilizers are characterized according to the solutions The method of the present invention obtained solutions from the fact that they do not have any have hypnotic side effects. In addition, the effects of the hormones, z. B. in cortisone, influenced favorably by the solubilizers.
Als Oxybenzoesäuren kommen solche in Frage, die eine oder mehrere Öxygruppen im Benzolkern enthalten. Insbesondere sind für das erfindungsgemäße Verfahren Mono- und Dioxybenzoesäuren geeignet, wobei. im letzteren Falle auch eine Oxygruppe veräthert sein kann. Beispielsweise seien genannt: 2-Oxybenzoesäure,2, 5-Dioxybenzoesäure, 2-Oxy-4-äthoxybenzoesäure. Die Säuren werden in Form ihrer Natriumsalze verwendet.Suitable oxybenzoic acids are those which have one or more Contain oxy groups in the benzene nucleus. In particular, are for the inventive method Mono- and dioxybenzoic acids suitable, with. in the latter case also an oxy group can be etherified. Examples include: 2-oxybenzoic acid, 2, 5-dioxybenzoic acid, 2-oxy-4-ethoxybenzoic acid. The acids are used in the form of their sodium salts.
Als in Wasser leicht lösliche Phenylmethylpyrazolone kommen zum Beispiel in Frage: i-Phenyl-2, 3-dimethylpyrazolon-(5), i-Phenyl-2, 5-dimethylpyrazolon-(3), i, 2-Dimethyl-3-phenylpyrazolon-(5), i-Phenyl-2, 3, 4-trimethylpyrazolon-(5), 1, 2, 4 - Trimethyl - 3 - phenylpyrazolon - (5), i-Phenyl-2, 3-dimethyl-4-aminopyrazolon-(5)",, 1, 2-Dimethyl-3-phenyl-4-aminopyrazolon-(5), i, 2-Dimethyl-3-phenyl-4-dimethylaminopyra.zolon-(5).Die Pyrazolonderivate können für sich allein oder auch in Mischung miteinander zur Anwendung kommen.Examples of phenylmethylpyrazolones which are readily soluble in water are in question: i-phenyl-2, 3-dimethylpyrazolon- (5), i-phenyl-2, 5-dimethylpyrazolon- (3), i, 2-Dimethyl-3-phenylpyrazolone- (5), i-phenyl-2, 3, 4-trimethylpyrazolone- (5), 1, 2, 4 - trimethyl - 3 - phenylpyrazolone - (5), i-phenyl-2, 3-dimethyl-4-aminopyrazolone- (5) ",, 1, 2-Dimethyl-3-phenyl-4-aminopyrazolone- (5), i, 2-dimethyl-3-phenyl-4-dimethylaminopyra.zolone- (5). The Pyrazolone derivatives can be used alone or mixed with one another come.
Die unerwartet große Verbesserung des Lösungsvermögens der erfindungsgemäß verwendeten Pyrazolone durch Zugabe von Salzen der Oxyben.zoesäure geht aus folgenden Lösungsversuchen hervor, wobei in allen Fällen stabile Lösungen erhalten werden: i a) 2o mg Cortisonacetat und 2,5 g 1, 2-Dimethyl-3-phenylpyra7-olon-(5) wurden miteiner entsprechenden Menge Wasser auf ein Volumen von 5 ccm aufgefüllt und earhitzt. b) 20 mg Cortisonacetat und 1,2gNatriumsalicylatwurden mit einerentsprechenden Menge Wasser auf ein Volumen von 5 ccm aufgefüllt und erhitzt. c) 40 mg Cortisonacetat, 1,5 g 1, 2-Dimethyl-3-phenylpyrazolon-(5) und i g Natriumsalicylat wurden mit der entsprechenden Menge Wasser auf ein Volumen von 5 ccm aufgefüllt und erhitzt.The unexpectedly large improvement in the solvency of the invention Pyrazolones used by adding salts of Oxyben.zoic acid result from the following Attempts at solving the problem result in stable solutions being obtained in all cases: i a) 20 mg of cortisone acetate and 2.5 g of 1,2-dimethyl-3-phenylpyra7-olon- (5) were made up to a volume of 5 cc with an appropriate amount of water and heated. b) 20 mg of cortisone acetate and 1.2 g of sodium salicylate were added with an appropriate amount Water made up to a volume of 5 ccm and heated. c) 40 mg of cortisone acetate, 1.5 g of 1, 2-dimethyl-3-phenylpyrazolon- (5) and i g of sodium salicylate were with the corresponding amount of water is made up to a volume of 5 ccm and heated.
2 a) 25 mg Progesteron und 2,5 g i, 2-Dimethyl-3 phenylpyrazolon-(5) wurden mit der entsprechenden Menge Wasser auf ein Volumen von 5 ccm aufgefüllt und erhitzt. b) 25 mg Progesteron und i g Natriumsalicylat wurden .mit der entsprechenden Menge Wasser auf ein Volumen von 5 ccm aufgefüllt und erhitzt. c) 5o mg Progesteron, o,5 g Dimethll-3-phenylpyrazolon-(5) und i g Natriumsalicylat wurden mit der entsprechenden Menge Wasser auf ein Volumen von 5 ccm gebracht und erhitzt.2 a) 25 mg progesterone and 2.5 g i, 2-dimethyl-3 phenylpyrazolone- (5) were made up to a volume of 5 ccm with the appropriate amount of water and heated. b) 25 mg progesterone and i g sodium salicylate were .with the appropriate Amount of water made up to a volume of 5 ccm and heated. c) 5o mg progesterone, 0.5 g of dimethyl-3-phenylpyrazolon- (5) and i g of sodium salicylate were treated with the corresponding Amount of water brought to a volume of 5 ccm and heated.
Aus diesen Lösungsversuchen ergibt sich, daß man bei erheblich geringerem Einsatz an Pyrazolon durch die Zugabe einer relativ kleinen Menge an Oxybenzoesäuresalz die doppelte Menge an Steroidhormon in Lösung bringen kann.From these attempts at a solution it follows that one with considerably less Use of pyrazolone by adding a relatively small amount of oxybenzoic acid salt can bring twice the amount of steroid hormone into solution.
Die Konzentration der Natriumsalze der Oxybenzoesäuren beträgt zweckmäßig zwischen etwa io und 30 1/m, die Konzentration der in Wasser leicht löslichen Pyrazolone ebenfalls etwa zwischen io und 300/0. Im allgemeinen richtet sich die Konzentration der Lösungsvermittler darnach, wieviel von den Steroidhormonen pro Volumeneinheit inLösung gebracht werden soll.The concentration of the sodium salts of oxybenzoic acids is expedient between about 10 and 30 1 / m, the concentration of the pyrazolones, which are readily soluble in water also roughly between io and 300/0. In general, the concentration is directed the solubilizer according to how much of the steroid hormones per unit volume should be brought into solution.
Den. Lösungen können auch andere in Wasser schwer lösliche Arzneimittel, wie beispielsweise i-Phenyl-2, 3-dimethyl-q.-dimethylaminopyrazolon-(5), zugefügt werden.The. Solutions can also contain other medicines that are poorly soluble in water, such as, for example, i-phenyl-2, 3-dimethyl-q.-dimethylaminopyrazolone- (5), added will.
Zweckmäßigerweise stellt man die Lösungen in folgender Weise her: Das Steroidhormon und eventuelle andere in Wasser schwer lösliche Zusätze werden zusammen mit dem Natriumsalz der Oxybenzoesäure in wenig Wasser heiß gelöst, darauf die anderen Lösungsvermittler zugegeben und mit Wasser auf das gewünschte Volumen aufgefüllt.The solutions are expediently prepared in the following way: The steroid hormone and any other additives that are sparingly soluble in water are used Dissolved hot together with the sodium salt of oxybenzoic acid in a little hot water, then the other solubilizers added and with water to the desired volume filled up.
Die gemäß dem-Verfahren der vorliegenden Erfindung hergestellten Lösungen,sind beständig und zeigen auch bei längerem Aufbewahren im Eisschrank keine Kristallabscheidung. Sie trüben sich beim Verdünnen mit Serum nicht und sind daher auch für intravenöse Injektionen .geeignet. Beispiel i 24 mg Corbisonacetat und 6oo mg Natriumsalicy lat werden in der Hitze in i ccm Wasser gelöst. Darauf gibt man goo mg i, 2-Dimethyl-3-phenylpyrazolon-(5) zu und füllt auf 3 ccm auf.The solutions made according to the method of the present invention are stable and show no crystal separation even when stored in the refrigerator for a long time. They do not become cloudy when diluted with serum and are therefore also suitable for intravenous use Injections .suitable. Example i 24 mg of corbison acetate and 600 mg of sodium salicy They are dissolved in 1 cc of water in the heat. Then goo mg of i, 2-dimethyl-3-phenylpyrazolone- (5) and fills up to 3 cc.
Sämtliche in den nachstehenden Beispielen angeführten Substanzen werden mit Wässer in der oben angegebenen Weise zu 3 ccm gelöst.All substances listed in the examples below are used 3 ccm dissolved with water in the manner indicated above.
Beispiel 2 15 mg Corbisonacetat, 6off-mg Natriumsalicylat, 6oo mg i, 2-Dimethyl-3-phenylpyrazolon-(5). Beispiel 3 i5 mg Cortisonacetat, 6oo mg Natriumsalicylat, 6oo mg 1, 2-Drmethyl-3-phenylpyrazolon-(5), 30o mg i-Phenyl-2, 3-dimethyl-4-dimethylaminopyrazolon-(5).Example 2 15 mg Corbison Acetate, 6off mg sodium salicylate, 600 mg i, 2-Dimethyl-3-phenylpyrazolone- (5). Example 3 15 mg of cortisone acetate, 6oo mg of sodium salicylate, 600 mg of 1,2-methyl-3-phenylpyrazolone- (5), 30o mg of i-phenyl-2,3-dimethyl-4-dimethylaminopyrazolone- (5).
Beispiel 4 18 mg Cortisonacetat, 6oo mg Natriumsalicylat, 9oo mg i-Phenyl-2, 3, 4-trimethylpyrazolon-(5). Beispiel 5 i5 mg Cortisonacetat, 6oo mg Natriumsalicylat, 900 mg 1, 2, 4-Trimethyl-3-phenylpyrazolon-(5), hergestellt nach dem Verfahren der deutschen Patentanmeldung F io299 IV c/i2 p. Beispiel 6 15 mg Cortisonacetat, 6 mg Desoxycorticosteronacetat, 60o mg Natriumsalicylat, 60o mg i, 2-Dimethyl-3-phenylpyrazolon-(5).Example 4 18 mg cortisone acetate, 6oo mg sodium salicylate, 9oo mg i-phenyl-2, 3, 4-trimethylpyrazolone- (5). Example 5 15 mg of cortisone acetate, 6oo mg of sodium salicylate, 900 mg of 1, 2, 4-trimethyl-3-phenylpyrazolon- (5), prepared by the process of German patent application F io299 IV c / i2 p. Example 6 15 mg of cortisone acetate, 6 mg deoxycorticosterone acetate, 60o mg sodium salicylate, 60o mg i, 2-dimethyl-3-phenylpyrazolone- (5).
Beispiel 7 15 mg Cortisonacetat, 60o mg Natriumsalicylat, 300 mg i, 2-Dimethyl-3-phenylpyrazolon-(5), 300 mg 1, a-Dimethyl-3-ghenyl-4-dimethylaminopyrazolon-Beispiel 8 15 mg Desoxycorticosteronacetat, 450 mg Natriumsalicylat, 60o mg 1, 2, 4-Trimethyl-3-phenylpyrazolon-(5).Example 7 15 mg cortisone acetate, 60o mg sodium salicylate, 300 mg i, 2-dimethyl-3-phenylpyrazolone- (5), 300 mg 1, α-dimethyl-3-ghenyl-4-dimethylaminopyrazolone Example 8 15 mg deoxycorticosterone acetate, 450 mg Sodium salicylate, 60o mg 1,2,4-trimethyl-3-phenylpyrazolone- (5).
Beispiel g 15 mg Desoxycorticosteronacetat, 60o mg Natriumsalicylat, 30o mg i, 2,Dimethyl-3-phenylpyrazolon-(5).Example g 15 mg deoxycorticosterone acetate, 60o mg sodium salicylate, 30o mg i, 2, dimethyl-3-phenylpyrazolone- (5).
Beispiel io 15 mg Desoxycortioosteronacetat, 450 mg Natriumsalicylat, 60o mg i, 2-Dirnethyl-3-phenylpyrazolon-(5).Example io 15 mg deoxycortioosterone acetate, 450 mg sodium salicylate, 60o mg of i, 2-dimethyl-3-phenylpyrazolone- (5).
Beispiel ii 15 mg Desoxycorticrosteronacetat, 60o mg Natriumsalicylat, 300m9 i-Phenyl-2, 3, 4-trimethylpyrazolon-(5).Example ii 15 mg deoxycorticrosterone acetate, 60o mg sodium salicylate, 300m9 i-phenyl-2,3,4-trimethylpyrazolone- (5).
Beispiel 12 15 mg Desoxycorticosteronacetat, 60o mg Natriumsalicylat, 300 mg i-Phenyl-2, 3, 4-trimethylpyrazolon-(5), 300 mg i-Phenyl-2, 3-dimethyl-4-dimethylaminopyrazolon-(5) . Example 12 15 mg deoxycorticosterone acetate, 60o mg sodium salicylate, 300 mg i-phenyl-2, 3, 4-trimethylpyrazolone- (5), 300 mg i-phenyl-2,3-dimethyl-4-dimethylaminopyrazolone- (5).
Beispiel 13 30 mg Progesteron, 450 mg Natriumsalicylat, 60o mg i, 2-Dimethyl-3-phenylpyrazolon-(5). Beispiel 14 30 mg Progesteron, 60o mg Natriumsalicylat 300 mg i, 2-Dimethyl-3-phenylpyrazolon-(5). Beispiel 15 30 mg Progesteron, 60o mg Natriumsalicylat, 450 mg i, 2, 4-Trimethyl-3-phenylpyrazolon-(5). Beispiel 16 30 mg Progesteron, 60o mg Natriumsalicylat, 60o mg i-Phenyl-2, 3-dimethylpyrazolon-(5). Beispiel 17 30 mg Progesteron, 60o mg gentisinsaures Natrium, 300m9 i, 2-Dimethyl-3-phenylpyrazolon-(5). Beispiel 18 30 mg Progesteron, 60o mg 2 - oxy - 4 - äthoxybenzoesaures Natrium, 30b mg i, 2-Dimethyl-3-phenylpyrazolon-(5).Example 13 30 mg progesterone, 450 mg sodium salicylate, 60o mg i, 2-dimethyl-3-phenylpyrazolone- (5). Example 14 30 mg progesterone, 60o mg sodium salicylate, 300 mg i, 2-dimethyl-3-phenylpyrazolone- (5). Example 15 30 mg progesterone, 60o mg sodium salicylate, 450 mg i, 2, 4-trimethyl-3-phenylpyrazolone- (5). Example 16 30 mg progesterone, 60o mg sodium salicylate, 60o mg i-phenyl-2,3-dimethylpyrazolone- (5). Example 17 30 mg of progesterone, 60o mg of sodium gentisate, 300m9, 2-dimethyl-3-phenylpyrazolone- (5). Example 18 30 mg of progesterone, 60o mg of 2-oxy-4-ethoxybenzoic acid sodium, 30 mg of i, 2-dimethyl-3-phenylpyrazolone- (5).
Beispiel ig 30 mg Tes.tasteron, 450 mg Natriumsalicylat, 300 mg 1, 2, 4-Trime-thyl-3-phenylpyrazolon-(5), 300 mg i-Phenyl-2, 3, 4-trimethylpyrazolon-(5).Example ig 30 mg Tes.tasteron, 450 mg sodium salicylate, 300 mg 1,2,4-trimethyl-3-phenylpyrazolone- (5), 300 mg i-phenyl-2,3,4-trimethylpyrazolone- (5).
Beispiel 2o 30 mg Testosteron, 500 mg Natriumsalicylat, 40o mg i, 2-Dimethyl-3-phenylpyrazolon-(5). Beispiel 21 30 mg Testosteron, 40o mg Natriumsalicylat, 500 mg 1, 2, 4-Tr.imethyl-3-phenylpyrazolon-(5).Example 2o 30 mg testosterone, 500 mg sodium salicylate, 40o mg i, 2-dimethyl-3-phenylpyrazolone- (5). Example 21 30 mg testosterone, 40o mg sodium salicylate, 500 mg 1, 2, 4-tri-methyl-3-phenylpyrazolone- (5).
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF10970A DE948184C (en) | 1953-01-31 | 1953-01-31 | Process for the production of aqueous solutions of steroid hormones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF10970A DE948184C (en) | 1953-01-31 | 1953-01-31 | Process for the production of aqueous solutions of steroid hormones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE948184C true DE948184C (en) | 1956-08-30 |
Family
ID=7086609
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEF10970A Expired DE948184C (en) | 1953-01-31 | 1953-01-31 | Process for the production of aqueous solutions of steroid hormones |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE948184C (en) |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE604228C (en) * | 1928-11-30 | 1934-10-17 | I G Farbenindustrie Akt Ges | Process for the preparation of easily soluble in water preparations of the salts of the china alkaloids which are difficult to dissolve or insoluble in water or of their aqueous solutions |
| DE649665C (en) * | 1932-09-29 | 1937-08-30 | Merz & Co | Process for the preparation of durable solutions from morphine hydrochloride for injection purposes |
| DE670089C (en) * | 1931-06-19 | 1939-01-11 | J D Riedel E De Haeen Akt Ges | Process for the preparation of durable injectable solutions of alkali barbiturates |
| DE677152C (en) * | 1938-06-30 | 1939-06-20 | Eggochemia Fabrik Chem U Pharm | Process for the production of aqueous quinidine salt solutions |
| DE709176C (en) * | 1937-12-08 | 1941-08-08 | Chemisch Pharmazeutische A G B | Process for the production of long-life aqueous solutions containing k-strophanthin, theophylline and grape sugar |
| DE718707C (en) * | 1940-06-29 | 1942-03-18 | Chemiewerk Homburg Ag | Process for the preparation of aqueous solutions of p-aminobenzene sulfonamide pyridine |
| CH221459A (en) * | 1940-05-25 | 1942-05-31 | Chemiewerk Homburg Aktiengesel | Process for the preparation of a solvent for theophylline. |
| FR880123A (en) * | 1941-04-03 | 1943-03-15 | Hoffmann La Roche | Process for the preparation of aqueous lactoflavin solutions |
| DE805769C (en) * | 1948-12-01 | 1951-05-28 | Vial & Uhlmann Inh Apoth E Rat | Process for the preparation of injectable solutions of guaiacol |
| DE832655C (en) * | 1950-12-28 | 1952-02-28 | Albert Ag Chem Werke | Process for the preparation of an injectable therapeutic agent containing copper and salicylic acid |
| DE835928C (en) * | 1950-02-05 | 1952-04-07 | Knoll Ag | Process for the preparation of concentrated aqueous solutions of 6-methylamino-2-methylheptane salicylate with an analgesic effect |
| DE862341C (en) * | 1943-05-15 | 1953-01-08 | Chemiewerk Homburg Ag | Process for the preparation of aqueous solutions of derivatives of p-aminobenzene sulfonamide |
-
1953
- 1953-01-31 DE DEF10970A patent/DE948184C/en not_active Expired
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE604228C (en) * | 1928-11-30 | 1934-10-17 | I G Farbenindustrie Akt Ges | Process for the preparation of easily soluble in water preparations of the salts of the china alkaloids which are difficult to dissolve or insoluble in water or of their aqueous solutions |
| DE670089C (en) * | 1931-06-19 | 1939-01-11 | J D Riedel E De Haeen Akt Ges | Process for the preparation of durable injectable solutions of alkali barbiturates |
| DE649665C (en) * | 1932-09-29 | 1937-08-30 | Merz & Co | Process for the preparation of durable solutions from morphine hydrochloride for injection purposes |
| DE709176C (en) * | 1937-12-08 | 1941-08-08 | Chemisch Pharmazeutische A G B | Process for the production of long-life aqueous solutions containing k-strophanthin, theophylline and grape sugar |
| DE677152C (en) * | 1938-06-30 | 1939-06-20 | Eggochemia Fabrik Chem U Pharm | Process for the production of aqueous quinidine salt solutions |
| CH221459A (en) * | 1940-05-25 | 1942-05-31 | Chemiewerk Homburg Aktiengesel | Process for the preparation of a solvent for theophylline. |
| DE718707C (en) * | 1940-06-29 | 1942-03-18 | Chemiewerk Homburg Ag | Process for the preparation of aqueous solutions of p-aminobenzene sulfonamide pyridine |
| FR880123A (en) * | 1941-04-03 | 1943-03-15 | Hoffmann La Roche | Process for the preparation of aqueous lactoflavin solutions |
| DE862341C (en) * | 1943-05-15 | 1953-01-08 | Chemiewerk Homburg Ag | Process for the preparation of aqueous solutions of derivatives of p-aminobenzene sulfonamide |
| DE805769C (en) * | 1948-12-01 | 1951-05-28 | Vial & Uhlmann Inh Apoth E Rat | Process for the preparation of injectable solutions of guaiacol |
| DE835928C (en) * | 1950-02-05 | 1952-04-07 | Knoll Ag | Process for the preparation of concentrated aqueous solutions of 6-methylamino-2-methylheptane salicylate with an analgesic effect |
| DE832655C (en) * | 1950-12-28 | 1952-02-28 | Albert Ag Chem Werke | Process for the preparation of an injectable therapeutic agent containing copper and salicylic acid |
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