US2855341A - Testosterone compositions - Google Patents
Testosterone compositions Download PDFInfo
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- US2855341A US2855341A US518738A US51873855A US2855341A US 2855341 A US2855341 A US 2855341A US 518738 A US518738 A US 518738A US 51873855 A US51873855 A US 51873855A US 2855341 A US2855341 A US 2855341A
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- Prior art keywords
- testosterone
- esters
- mixture
- undecylenate
- valerate
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- 239000000203 mixture Substances 0.000 title claims description 27
- 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 title claims description 22
- 229960003604 testosterone Drugs 0.000 title claims description 13
- 230000001548 androgenic effect Effects 0.000 claims description 12
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 claims description 9
- 229960001712 testosterone propionate Drugs 0.000 claims description 9
- 229940070710 valerate Drugs 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- PBFYIQCFOZXSKC-CNQKSJKFSA-N [(8r,9s,10r,13s,14s,17s)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] undec-10-enoate Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)OC(=O)CCCCCCCCC=C)[C@@H]4[C@@H]3CCC2=C1 PBFYIQCFOZXSKC-CNQKSJKFSA-N 0.000 description 11
- UCNQPYVHDCHENM-CGRIZKAYSA-N [(8r,9s,10r,13s,14s,17s)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] pentanoate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 UCNQPYVHDCHENM-CGRIZKAYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- -1 undecylenyl Chemical group 0.000 description 6
- 150000003515 testosterones Chemical class 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- PSEVKFKRYVAODC-UHFFFAOYSA-N 11-chloroundec-1-ene Chemical compound ClCCCCCCCCCC=C PSEVKFKRYVAODC-UHFFFAOYSA-N 0.000 description 1
- 206010006240 Breast engorgement Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 208000007106 menorrhagia Diseases 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229940075466 undecylenate Drugs 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
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
Definitions
- compositions having androgenic properties relate to compositions having androgenic properties.' More particularly, this invention is concerned with compositions having androgenic properties comprising mixtures of testosterone undecylenate, -testosterone valerate and testosteronepropionate.
- esters of testosterone moreparticularly-the propionate have been widely used in recent years in the treatment of androgenic disorders. ⁇ They have been found to be primarily useful in testicular hormone ⁇ .'deciency of the male, and forthis reason are offvalue in the treatment of prepuberal and postpuberal e'unuchoidismA and hypogonadism; Other notable examples of valuable applications of thesetestosterone esters are in the treatment of the female in the control of menorrhagia and in post-partum inhibition of lactation and breast engorgement. t I
- mixtures rof the above-mentioned esters of testosterone in an approximate ratio of l :8:2 parts respectively are preferable.
- the content of the testosterone ester mixture in a preparation may vary between 0.01 to 50% by weight.
- a single dosage unit may contain a quantity varying from 0.5 to 500 mg. of the testosterone ester mixture.
- (l) l dose of the testosterone ester mixture according to the present invention consisting of 1.5 mg. of testosterone undecylenate 0.8 mg. of testosterone valerate 0.2 mg. of testosterone propionate Total 2.5 mg. mixture (2) l dose of 2.5 mg. of testosterone undecylenate alone,
- the new testosterone ester preparations are prepared by conventional methods, for example withthe. use of pharmaceutical, organic or ⁇ inorganic carrier materials such as are suitable for parenteral, oral or topical application. Such substances are concerned as do not react with the testosterone esters, as for example water, vegetable oils, benzyl alcohols, polyethylene glycols, gelatin, lactose, starch, magnesium stearate, talc, vaseline, cholesterol or other medicament carriers. Of especial importance are preparations for parenteral administration, preferably solutions, primarily oil solutions, and also suspensions, emulsions or implantates; in a corresponding manner tablets or drageesare produced for oral administration and salves or creams for topical application.
- pharmaceutical, organic or ⁇ inorganic carrier materials such as are suitable for parenteral, oral or topical application.
- Such substances are concerned as do not react with the testosterone esters, as for example water, vegetable oils, benzyl alcohols, polyethylene glycols, gelatin, lactose, starch, magnesium
- the preparationsv can be sterilized or subjected to the addition of auxiliary materials such as preserving, stabilizing, wetting or emulsifying agents, salts for variation of the osmotic pressure or buffer substances or also other therapeutically valuable materials, for example, local anaesthetics or substances having an effect upon the blood vessels.
- auxiliary materials such as preserving, stabilizing, wetting or emulsifying agents, salts for variation of the osmotic pressure or buffer substances or also other therapeutically valuable materials, for example, local anaesthetics or substances having an effect upon the blood vessels.
- EXAMPLE 2 The testosterone Yesters are ground with sterile poly-- oxyethylene sorbitane ⁇ monolaurate and a small partof the suspension-agentadded in portions. The desired volume is made up with the remainder of the suspension agent.
- the suspension agent is prepared by dissolving the sodium carboxymethylcellulose in a quantity of distilled water Vand'dissolving vtherein theprimary and secondary sodium phosphate, the thimerosal and the sodium chloride. Before use, the suspension agent is heat-sterilized. The preparation and lling of the crystal ampoules is carried out-under aseptic conditions.
- the testosterone esters to be used according to this invention can be produced by known methods.
- the testosterone undecylenate is obtained in the following manner:
- the ether extract is washed consecutively with 0.5N-sulfuric acid, water, 0.1 N-caustic soda solution and with water to a neutral reaction, dried with sodiu'msulfate and evaporated.
- the solvent-free residue is recrystallizedfrom anhydrous ethanol with cooling in a mixture of ice and common salt. By liltration with suction, washing with ethanol and drying at 25-28 C. under vacuum, pure testosterone undecylenate of the is obtained in colorless crystals of M. P. 52-53.5 C.
- composition having androgenic properties comprising testosterone undecylenate, testosterone valerate and testosterone propionate in an approximate ratio of 15 :8:2 parts by weight respectively.
- composition having androgenic properties comprising testosterone undecylenate, testosterone valerate and testosterone popionate in an approximate ratio of 15 :8:2 parts by weight respectively in a pharmaceutical carrier;
- a composition having androgenic properties comprising from 0.01 percent by weight to 50 percent by weight of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in an approximate ratio of 15:8:2 parts by weight respectively in a pharmaceutical carrier.
- a composition having androgenic properties in dosage unit form comprisingfrom 0.5 to 500 mg. of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in a ratio of l5 :8:2 parts by weight and a sterile parenteral aqueous diluent.
- a composition having androgenic properties in dosage unit form comprising from 0.5 to 500 mg. of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in a ratio of 15:8:2 parts by weight and a sterile parenteral oily diluent.
- a composition having androgenic properties in dosage unit form comprising from 0.5 to 500 mg. of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in a ratio of l5 8 :2 parts by weight and a solid pharmaceutical carrier, said composition being in tablet dosage unit form.
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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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Oct. 7, l1958 R. MEIER ET AL TEsTosTERoNE con/(POSITIONS United `States Patent O 2,855,341 l y y TEsTosrERoNE coMPoslTIoNs Rolf Meier and Albert Wettstein, Basel, and Emil Lang, Riehen, Switzerland, assignors to Ciba Pharmaceutical Products Inc., Summit, N. J.
Application June 29, 1955, Serial l`vo.l,i18,7 38 Claims priority, application,Switzerland'luly 2, 1954 6 claims. (ci. 1mg-74) This invention relates to compositions having androgenic properties.' More particularly, this invention is concerned with compositions having androgenic properties comprising mixtures of testosterone undecylenate, -testosterone valerate and testosteronepropionate.
Various esters of testosterone moreparticularly-the propionate, have been widely used in recent years in the treatment of androgenic disorders.` They have been found to be primarily useful in testicular hormone`.'deciency of the male, and forthis reason are offvalue in the treatment of prepuberal and postpuberal e'unuchoidismA and hypogonadism; Other notable examples of valuable applications of thesetestosterone esters are in the treatment of the female in the control of menorrhagia and in post-partum inhibition of lactation and breast engorgement. t I
Among the least desirable aspects of ladministering these Vhormones from a clinical point of viewis the necessity for frequent administration in order to obtain a sustained drug eiect. In addition, in order to obtain a rapid onset, it is frequently necessary to administer extremely high doses. When the drugsare administered parenterally, as is frequentlythe case, the discomfort and pain associated with-such administration become extremely mportant-factorsfrom the viewpoint of both the physician and the patient. i f
We have now discovered thatwhen the undecylenyl, valeryl and propionyl esters of testosteroneV are combined in a mixture, the resultant composition is capable of effecting a rapid and protracted androgenic effect, not previously obtainable upon the administration of any .of these esters singularly.
Although the undecylenyl, valeryl and propionyl esters of testosterone may be combined in various proportions to obtain rapid and protracted' androgenic effects,v we
have found that mixtures rof the above-mentioned esters of testosterone in an approximate ratio of l :8:2 parts respectively are preferable. The content of the testosterone ester mixture in a preparation may vary between 0.01 to 50% by weight. A single dosage unit may contain a quantity varying from 0.5 to 500 mg. of the testosterone ester mixture.
The special therapeutic properties of the new hormone preparations can be proved, for example, by experiments on capons. For this purpose, by way of example indivdual doses of 2.5 mg. were administered intramuscularly as follows:
(l) l dose of the testosterone ester mixture according to the present invention, consisting of 1.5 mg. of testosterone undecylenate 0.8 mg. of testosterone valerate 0.2 mg. of testosterone propionate Total 2.5 mg. mixture (2) l dose of 2.5 mg. of testosterone undecylenate alone,
(3) l dose of 2.5 mg. of testosterone valerate alone,
(4) l dose of 2.5 mg. of testosterone propionate alone.
, i ,Y Patented Oct. 7, 1958 ICC The silhouette of the comb `was measured planimetrically and the growth expressed graphically las a percentage as shown in the accompanying drawing. 'Ihe individual curves represent average values of experiments with 4 to 7 capons. It is seen from them that a single dose of the mixture of they three testosterone esters according to this invention has a considerably stronger effect than that of any of the esters alone in the same dosage. A further particularA advantage of the new preparations consists in that, when compared with the individual esters, they have Ia more rapid onset and attainment of the maximum growth and a more protracted maximum growth.
The new testosterone ester preparations are prepared by conventional methods, for example withthe. use of pharmaceutical, organic or` inorganic carrier materials such as are suitable for parenteral, oral or topical application. Such substances are concerned as do not react with the testosterone esters, as for example water, vegetable oils, benzyl alcohols, polyethylene glycols, gelatin, lactose, starch, magnesium stearate, talc, vaseline, cholesterol or other medicament carriers. Of especial importance are preparations for parenteral administration, preferably solutions, primarily oil solutions, and also suspensions, emulsions or implantates; in a corresponding manner tablets or drageesare produced for oral administration and salves or creams for topical application. If desired, the preparationsv can be sterilized or subjected to the addition of auxiliary materials such as preserving, stabilizing, wetting or emulsifying agents, salts for variation of the osmotic pressure or buffer substances or also other therapeutically valuable materials, for example, local anaesthetics or substances having an effect upon the blood vessels.
The following examples illustrate the invention:
EXAMPLE l )Oil ampoules` Benzyl alcol1o1 A 40 Sesame oil to 1 cc; t
The production of these` oil ampoules can be carried out as follows: v n
(I) The testosterone esters (undecylenate, valerate, propionate) are` mixed ,and ,finely ground. Then the benzyl alcohol is introduced Vand the whole heated on the water bath until solution results.
(II) The solution I is then diluted with sesame oil, so that l cc. of the resulting solution contains exactly 250 mg. of the testosterone esters.
(III) The solution is filtered in the customary manner and lilled into ampoules; the closes ampoules are heatsterilized by autoclaving with steam under pressure in accordance with the usual directions.
EXAMPLE 2 The testosterone Yesters are ground with sterile poly-- oxyethylene sorbitane `monolaurate and a small partof the suspension-agentadded in portions. The desired volume is made up with the remainder of the suspension agent. The suspension agent is prepared by dissolving the sodium carboxymethylcellulose in a quantity of distilled water Vand'dissolving vtherein theprimary and secondary sodium phosphate, the thimerosal and the sodium chloride. Before use, the suspension agent is heat-sterilized. The preparation and lling of the crystal ampoules is carried out-under aseptic conditions.
(I) The hormones are ground to a homogeneous mixture with a part of the lactose; mixing is then carried out with'the remainder of the lactose and the powdered sugar.
(II) The p-s'tearoylamino-phenyl-trimethylammonium methyl sulfate'is dissolved in three times its weight of alcohol and the hormone-powder mixture I moistened with the solution, granulated with a little water and dried.
(III) The lubricant is added and the whole tableted in units of appropriate dosage (supra).
The testosterone esters to be used according to this invention can be produced by known methods. Thus for example, the testosterone undecylenate is obtained in the following manner:
Into a solution, prepared in a dry nitrogen atmosphere, of 28.84 gm. of testosterone in 100 cc. of anhydrous benzene and 30.2 cc. of anhydrous pyridine, 27.0 cc. of undecylenyl chloride are introduced drop-Wise within 45 minutes with stirring and external cooling with water at 18-20 C. When the addition is complete, the mixture is stirred for a further hours at room temperature, then poured into 200 cc. of 2 N-sulfuric acid and the Whole extracted with ether. The ether extract is washed consecutively with 0.5N-sulfuric acid, water, 0.1 N-caustic soda solution and with water to a neutral reaction, dried with sodiu'msulfate and evaporated. The solvent-free residue is recrystallizedfrom anhydrous ethanol with cooling in a mixture of ice and common salt. By liltration with suction, washing with ethanol and drying at 25-28 C. under vacuum, pure testosterone undecylenate of the is obtained in colorless crystals of M. P. 52-53.5 C.
What is claimed is:
1. A composition having androgenic properties comprising testosterone undecylenate, testosterone valerate and testosterone propionate in an approximate ratio of 15 :8:2 parts by weight respectively.
2. A composition having androgenic properties comprising testosterone undecylenate, testosterone valerate and testosterone popionate in an approximate ratio of 15 :8:2 parts by weight respectively in a pharmaceutical carrier;
3. A composition having androgenic properties comprising from 0.01 percent by weight to 50 percent by weight of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in an approximate ratio of 15:8:2 parts by weight respectively in a pharmaceutical carrier.
4. A composition having androgenic properties in dosage unit formcomprisingfrom 0.5 to 500 mg. of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in a ratio of l5 :8:2 parts by weight and a sterile parenteral aqueous diluent.
5. A composition having androgenic properties in dosage unit form comprising from 0.5 to 500 mg. of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in a ratio of 15:8:2 parts by weight and a sterile parenteral oily diluent.
6. A composition having androgenic properties in dosage unit form comprising from 0.5 to 500 mg. of a mixture of testosterone undecylenate, testosterone valerate and testosterone propionate in a ratio of l5 8 :2 parts by weight and a solid pharmaceutical carrier, said composition being in tablet dosage unit form.
OTHER REFERENCES Miescher: Biochem. I.,`vo1. 30, 1936, pp. 1977-1990. Parkes: I. of Endocrinology, vol. 4, 1944-45, p. 102.
Claims (1)
1. A COMPOSITION HAVING ANDROGENIC PROPERTIED COMPRISING TESTOSTERONE UNDERCYLENATE, TESTTOSTERONE VALERATE AND TESTOSTERONE PROPIONATE IN AN APPOROXIMATE RATIO OF 15:8:2 PARTS BY WEIGHT RESPECTIVELY.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2855341X | 1954-07-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2855341A true US2855341A (en) | 1958-10-07 |
Family
ID=4572317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US518738A Expired - Lifetime US2855341A (en) | 1954-07-02 | 1955-06-29 | Testosterone compositions |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2855341A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2930695A (en) * | 1956-02-23 | 1960-03-29 | Rosner Hixson Lab Inc | Animal feed supplement |
| US2960407A (en) * | 1958-05-14 | 1960-11-15 | Olin Mathieson | Diethylstilbestrol compositions |
| US3198805A (en) * | 1961-10-30 | 1965-08-03 | Roussel Uclaf | A-nor-b-homo-steroids having isoxazole substituent and process of preparation |
| DE2508615A1 (en) * | 1974-02-28 | 1975-09-04 | Akzo Nv | PRODUCTS WITH ANDROGENIC EFFECTIVENESS FOR ORAL ADMINISTRATION |
| US4039669A (en) * | 1975-08-01 | 1977-08-02 | Sterling Drug Inc. | Composition for topical application and use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2675342A (en) * | 1950-09-30 | 1954-04-13 | Schering Corp | Supersaturated oil solutions of steroid hormones |
-
1955
- 1955-06-29 US US518738A patent/US2855341A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2675342A (en) * | 1950-09-30 | 1954-04-13 | Schering Corp | Supersaturated oil solutions of steroid hormones |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2930695A (en) * | 1956-02-23 | 1960-03-29 | Rosner Hixson Lab Inc | Animal feed supplement |
| US2960407A (en) * | 1958-05-14 | 1960-11-15 | Olin Mathieson | Diethylstilbestrol compositions |
| US3198805A (en) * | 1961-10-30 | 1965-08-03 | Roussel Uclaf | A-nor-b-homo-steroids having isoxazole substituent and process of preparation |
| DE2508615A1 (en) * | 1974-02-28 | 1975-09-04 | Akzo Nv | PRODUCTS WITH ANDROGENIC EFFECTIVENESS FOR ORAL ADMINISTRATION |
| US4039669A (en) * | 1975-08-01 | 1977-08-02 | Sterling Drug Inc. | Composition for topical application and use thereof |
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