US20040033999A1 - Testosterone derivative - Google Patents
Testosterone derivative Download PDFInfo
- Publication number
- US20040033999A1 US20040033999A1 US10/177,989 US17798902A US2004033999A1 US 20040033999 A1 US20040033999 A1 US 20040033999A1 US 17798902 A US17798902 A US 17798902A US 2004033999 A1 US2004033999 A1 US 2004033999A1
- Authority
- US
- United States
- Prior art keywords
- compound
- testosterone
- androgen
- administration
- ment
- 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.)
- Abandoned
Links
- WRLOOHHQBLTCLM-QKLCDPPYSA-N [H][C@@]12CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3C[C@@H](C)[C@@]21[H] Chemical compound [H][C@@]12CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3C[C@@H](C)[C@@]21[H] WRLOOHHQBLTCLM-QKLCDPPYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
- C07J1/0074—Esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
Definitions
- the invention is in the field of androgenic hormones, more specifically derivatives of testosterone.
- Testosterone derivatives are known. Testosterone itself, the natural male hormone, has many known drawbacks as far as methods of administration are concerned. It has a short-lasting activity, is insoluble in the usual pharmaceutically acceptable media, and is not very potent. The more potent dihydrotestosterone (5 ⁇ -reduced form of testosterone) is considered a health-risk, notably for the prostate. A somewhat better soluble derivative is testosterone undecanoate, which is known as the active substance in the product Andriol®.
- male contraception may comprise a regimen of administration of hormones in which a progestagen serves to achieve a contraceptive effect and an androgen serves to supplement the resulting decreased testosterone level.
- a progestagen serves to achieve a contraceptive effect
- an androgen serves to supplement the resulting decreased testosterone level.
- male contraception is performed with an androgenic hormone alone.
- the regular androgen intake needed for this requires androgens which are improved as to potency and duration of action, and for which a practical way of administration is available.
- the invention is the compound (7 ⁇ ,17 ⁇ )-7-methyl-17-[(1-oxoundecyl)oxy]estr-4-en-3-one, which has the following structural formula:
- the compound of the invention is also to be referred to as 7 ⁇ -methyl-19-nortestosterone undecanoate, in short MENT undecanoate.
- the compound of the invention can be prepared by esterification of the 17-OH group of MENT with undecanoic acid or derivatives thereof. This esterification may be carried out using methods well known in the art or readily available from the chemical literature, for example, using methods and catalysts described in Advanced Organic Chemistry, J. March, 4th Ed, pages 1281-1282, 1992. MENT can be prepared as disclosed in FR 4.521 M and U.S. Pat. No. 5,342,834.
- the invention also pertains to the compound MENT undecanoate as a medicine.
- the compound of the invention being a potent androgen, it can be used in, inter alia, male contraception and male or female hormone replacement therapy.
- the invention also pertains to a method of treatment of androgen insufficiency, by administering to a human male or female an effective amount of MENT undecanoate.
- the invention also is in the use of MENT undecanoate for the preparation of a medicine for treating androgen insufficiency.
- the term “androgen insufficiency” is to be understood to pertain to all kinds of diseases, disorders, and symptoms in which a male or a female suffers from too low a testosterone level, such as in hypogonadal men.
- the androgen insufficiency to be treated by the compound of the invention is the reduction of the testosterone level which a human male incurs as a result of age (the compound of the invention is then used for male hormone replacement therapy), or when he is subject to male contraception.
- the compound of the invention especially serves to neutralise the effect of regimens of male hormone contraception in which a sterilitant such as a progestagen or LHRH (luteinizing hormone releasing hormone) is administered regularly, e.g. daily, or it is used as the sole male contraceptive substance.
- a sterilitant such as a progestagen or LHRH (luteinizing hormone releasing hormone) is administered regularly, e.g. daily, or it is used as the sole male contraceptive substance.
- the invention also relates to pharmaceutical formulations comprising MENT undecanoate and a pharmaceutically acceptable carrier.
- the carrier may be in a solid form or liquid form
- the formulation may be an oral dosage unit such as a tablet or, preferably, an oral solution, e.g. in a capsule.
- Methods and compositions for making such dosage units are well-known to those skilled in the art. For example, conventional techniques for making tablets and pills, containing active ingredients, are described in the standard reference, Gennaro et al, Remington's Pharmaceutical Sciences, (18th ed., Mack Publishing Company, 1990, see especially Part 8: Pharmaceutical Preparations and Their Manufacture).
- the compound can also be administered via an implant, a patch, or any other suitable device for the sustained release of an androgen composition.
- the preferred oral dosage unit is that of a capsule containing the compound of the invention taken up in a liquid medium as described below.
- the preferred injection device is a needleless injection system, e.g. as described in U.S. Pat. No. 5,599,302.
- the compound may also be suspended in an aqueous medium, but the above solutions in oil are preferred.
- Methods and compositions for making liquids suitable for parenteral administration are known in the art, see e.g. Remington's, pages 1545 ff.
- any capsule made from a pharmaceutically acceptable wall material can be employed.
- Methods and compositions for making capsules suitable for oral administration are known in the art, see e.g. Remington's, pages 1658 ff.
- a preferred material is a softgel such as used for Andriol® capsules.
- the invention also pertains to a method of treatment of androgen insufficiency, by administering to a human male, by injection or by means of an oral dosage unit, an effective amount of MENT undecanoate dissolved in a pharmaceutically acceptable oil.
- the invention also is in the use of MENT undecanoate for the preparation of a medicine for treating androgen insufficiency by injecting into a human male an effective amount of MENT undecanoate dissolved in a pharmaceutically acceptable oil, or by orally administering such an oily solution.
- the dose of and regimen of administration MENT undecanoate, or a pharmaceutical composition thereof, to be administered will obviously depend on the therapeutic effect to be achieved and will vary with the route of administration, and the age and condition of the individual subject to whom the medicament is to be administered, and/or or the particular contraceptive or HRT regimen in which it is used. Typical doses are 100 mg or more per three months upon intramuscular administration and 50-250 mg, more preferably 80 mg per day upon oral administration.
- the RDP is determined as follows: Solubility ⁇ ⁇ of ⁇ ⁇ compound Solubility ⁇ ⁇ of ⁇ ⁇ testosterone ⁇ ⁇ potency ⁇ ⁇ of ⁇ ⁇ compound ⁇ ⁇ relative ⁇ ⁇ to ⁇ ⁇ that ⁇ ⁇ of ⁇ ⁇ testosterone TABLE 1 solubility solubility compound arachis oil oleic acid testosterone ⁇ 0.1 mg/ml ⁇ 25 mg/ml MENT ⁇ 0.1 mg/ml ⁇ 15 mg/ml testosterone undecanoate ⁇ 45 mg/ml 200-250 mg/ml MENT undecanoate >200 mg/ml ⁇ 500 mg/ml
Abstract
The invention is the novel androgen (7α,17β)-7-methyl-17-[(1-oxoundecyl)oxy]estr-4en-3one (MENT undecanoate). This compound distinguishes favourably from other testosterone derivatives in that it has a good solubility in oily media. It particularly exhibits a good dissolved potency relative to testosterone. The compound is particularly suitable for administration by means of injection.
Description
- The invention is in the field of androgenic hormones, more specifically derivatives of testosterone.
- Testosterone derivatives are known. Testosterone itself, the natural male hormone, has many known drawbacks as far as methods of administration are concerned. It has a short-lasting activity, is insoluble in the usual pharmaceutically acceptable media, and is not very potent. The more potent dihydrotestosterone (5α-reduced form of testosterone) is considered a health-risk, notably for the prostate. A somewhat better soluble derivative is testosterone undecanoate, which is known as the active substance in the product Andriol®.
- More potent androgens are 7α-methyl-19-nortestosterone (MENT) and related compounds, such as disclosed in FR 4.521 M and U.S. Pat. No. 5,342,834. However, MENT suffers from a bad solubility and short duration of action.
- New androgenic hormones are needed which inter alia satisfy the demands connected with new areas of interest, such as male contraception and male HRT (hormone replacement therapy). Thus, e.g., male contraception may comprise a regimen of administration of hormones in which a progestagen serves to achieve a contraceptive effect and an androgen serves to supplement the resulting decreased testosterone level. Another option is that male contraception is performed with an androgenic hormone alone. The regular androgen intake needed for this requires androgens which are improved as to potency and duration of action, and for which a practical way of administration is available. As low a frequency of administration being desired, there is a demand for androgens which have such physico-chemical properties as to be rendered into a solution, particularly a solution by which the androgen can be administered via injection, preferably once a week or less frequent, or orally via a capsule to be taken, e.g., daily. This means that a basic desired property for a novel androgen is that it has an improved solubility in one or more pharmaceutically acceptable liquids.
- Even more desired is an androgen which has a favourable relationship of potency and solubility, as a weak androgen will require more of it to be dissolved in order to attain the same activity as a more potent androgen. This means an androgen having an improved relative “dissolved potency”, hereinafter referred to as RDP, wherein the RDP of a given androgen in a given medium is the product of its androgenic potency relative to that of the natural male hormone testosterone and its solubility in the medium relative to that of testosterone.
-
- The compound of the invention is also to be referred to as 7α-methyl-19-nortestosterone undecanoate, in short MENT undecanoate.
- The compound of the invention has a significantly better solubility than could be expected on the basis of the known testosterone derivatives. Moreover, the compound of the invention has a surprisingly higher RDP than the known compounds.
- The compound of the invention can be prepared by esterification of the 17-OH group of MENT with undecanoic acid or derivatives thereof. This esterification may be carried out using methods well known in the art or readily available from the chemical literature, for example, using methods and catalysts described in Advanced Organic Chemistry, J. March, 4th Ed, pages 1281-1282, 1992. MENT can be prepared as disclosed in FR 4.521 M and U.S. Pat. No. 5,342,834.
- The invention also pertains to the compound MENT undecanoate as a medicine. The compound of the invention being a potent androgen, it can be used in, inter alia, male contraception and male or female hormone replacement therapy. Thus the invention also pertains to a method of treatment of androgen insufficiency, by administering to a human male or female an effective amount of MENT undecanoate. The invention also is in the use of MENT undecanoate for the preparation of a medicine for treating androgen insufficiency. In the context of the invention, the term “androgen insufficiency” is to be understood to pertain to all kinds of diseases, disorders, and symptoms in which a male or a female suffers from too low a testosterone level, such as in hypogonadal men. In particular, the androgen insufficiency to be treated by the compound of the invention is the reduction of the testosterone level which a human male incurs as a result of age (the compound of the invention is then used for male hormone replacement therapy), or when he is subject to male contraception. In the context of male contraception, the compound of the invention especially serves to neutralise the effect of regimens of male hormone contraception in which a sterilitant such as a progestagen or LHRH (luteinizing hormone releasing hormone) is administered regularly, e.g. daily, or it is used as the sole male contraceptive substance.
- The invention also relates to pharmaceutical formulations comprising MENT undecanoate and a pharmaceutically acceptable carrier. Thus the carrier may be in a solid form or liquid form, and the formulation may be an oral dosage unit such as a tablet or, preferably, an oral solution, e.g. in a capsule. Methods and compositions for making such dosage units are well-known to those skilled in the art. For example, conventional techniques for making tablets and pills, containing active ingredients, are described in the standard reference, Gennaro et al, Remington's Pharmaceutical Sciences, (18th ed., Mack Publishing Company, 1990, see especially Part 8: Pharmaceutical Preparations and Their Manufacture). The compound can also be administered via an implant, a patch, or any other suitable device for the sustained release of an androgen composition. The preferred oral dosage unit is that of a capsule containing the compound of the invention taken up in a liquid medium as described below.
- In order to benefit most from the compound's androgenic activity, administration of the compound dissolved in an oil is preferred, i.e. either orally as above, and notably via (intramuscular) injection. MENT undecanoate has a solubility in oily media, which makes it particularly suitable for a liquid pharmaceutical formulation comprising MENT undecanoate dissolved in a pharmaceutically acceptable oil. Suitable oils are, e.g., arachis oil, oleic acid, ricinus oil, sesam oil and the like. Arachis oil is preferred.
- For injection the preferred injection device is a needleless injection system, e.g. as described in U.S. Pat. No. 5,599,302. To this end the compound may also be suspended in an aqueous medium, but the above solutions in oil are preferred. Methods and compositions for making liquids suitable for parenteral administration are known in the art, see e.g. Remington's, pages 1545 ff.
- For oral administration, any capsule made from a pharmaceutically acceptable wall material can be employed. Methods and compositions for making capsules suitable for oral administration are known in the art, see e.g. Remington's, pages 1658 ff. A preferred material is a softgel such as used for Andriol® capsules.
- The invention also pertains to a method of treatment of androgen insufficiency, by administering to a human male, by injection or by means of an oral dosage unit, an effective amount of MENT undecanoate dissolved in a pharmaceutically acceptable oil. The invention also is in the use of MENT undecanoate for the preparation of a medicine for treating androgen insufficiency by injecting into a human male an effective amount of MENT undecanoate dissolved in a pharmaceutically acceptable oil, or by orally administering such an oily solution.
- The dose of and regimen of administration MENT undecanoate, or a pharmaceutical composition thereof, to be administered will obviously depend on the therapeutic effect to be achieved and will vary with the route of administration, and the age and condition of the individual subject to whom the medicament is to be administered, and/or or the particular contraceptive or HRT regimen in which it is used. Typical doses are 100 mg or more per three months upon intramuscular administration and 50-250 mg, more preferably 80 mg per day upon oral administration.
- The invention will be further explained hereinafter with reference to the following Examples.
- (7α,17β)-7-Methyl-17-[(1-oxoundecyl)oxy]estr-4-en-3-one.
- A total of 2.23 grams of commercially available undecanoyl chloride were added to a stirred solution of 1.58 grams of (7α,17β)-17-hydroxy-7-methylestr-4-en-3-one at 0-5° C. The reaction mixture was allowed to reach room temperature and stirred overnight. Thereafter, ice was added and after stirring for another 2 hours the reaction mixture was poured into ice-water, containing 4 ml of conc. H2SO4, followed by ethyl acetate extraction. The organic layers were washed with water, cold 1 N NaOH solution and brine, dried on sodium sulfate, filtered and evaporated in vacuo. The residue was chromatographed over silica. Elution with heptane-ethylacetate (4:1) and evaporation gave a greasy solid that was collected. Yield 1.42 g, [α]D 20=+36° (c=1; dioxane), MS (ESI): 456.
- (17β)-17-[(1-Oxoundecyl)oxy]androst-4-en-3-one
- “Testosterone undecanoate” is commercially available.
- About 20-30 mgs of compound were powdered and then dissolved in as little solvent as necessary to dissolve all the visible particles. Dissolution was accomplished by heating in a waterbath of 50° C. and shaking on a Vortex™ shaker for 15 minutes. The solubility was calculated by determining the amount of compound (in mg) dissolved per ml of solvent.
- The solubility and the androgenic potency of the compound of the invention and three reference compounds was used to determine RDP. The results are given in the tables below. With regard to clinically desirable anabolic and antigonadotropic effects (androgenic effects), MENT is ten times more potent than testosterone in rats (Kumar N et al, Endocrinology 130: 3677-3683 (1992) and J Steroid Biochem Molec Biol 52: 105-112 (1995)) and monkeys (Cummings D et al, J Clin Endocrinol Metab 83, 4212-4219 (1998)). The RDP is determined as follows:
TABLE 1 solubility solubility compound arachis oil oleic acid testosterone <<0.1 mg/ml ˜25 mg/ml MENT ≦0.1 mg/ml ˜15 mg/ml testosterone undecanoate ˜45 mg/ml 200-250 mg/ml MENT undecanoate >200 mg/ml ≧500 mg/ml - From the table it can be learned that the solubility of MENT undecanoate in arachis oil is much better than that of any of the other androgens. The solubility of MENT undecanoate in oleic acid is also better than expected in view of that of the known androgens.
Claims (2)
1. A kit for male contraception, comprising:
a means for the administration of a progestagen and
a means for the administration of an androgen,
wherein the latter means is a pharmaceutical formulation, comprising:
(7α,17β)-7-methyl-17-[(1-oxoundecyl)oxy]estr-4-en-3-one and
a pharmaceutically acceptable carrier.
2. The kit for male contraception according to claim 1 , wherein the pharmaceutically acceptable carrier is a liquid in which (7α,17β)-7-methyl-17-[(1-oxoundecyl)oxy]estr-4-en-3-one is dissolved.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/177,989 US20040033999A1 (en) | 1998-06-19 | 2002-06-21 | Testosterone derivative |
US10/964,076 US6989378B2 (en) | 1998-06-19 | 2004-10-13 | Testosterone derivative |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98202052.1 | 1998-06-19 | ||
EP98202052 | 1998-06-19 | ||
US09/719,927 US6437158B1 (en) | 1998-06-19 | 1999-06-14 | Testosterone derivative |
US10/177,989 US20040033999A1 (en) | 1998-06-19 | 2002-06-21 | Testosterone derivative |
Related Parent Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/719,927 Division US6437158B1 (en) | 1998-06-19 | 1999-06-14 | Testosterone derivative |
US09719927 Division | 1999-06-14 | ||
PCT/EP1999/004102 Division WO1999067271A1 (en) | 1998-06-19 | 1999-06-14 | Testosterone derivative |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/964,076 Division US6989378B2 (en) | 1998-06-19 | 2004-10-13 | Testosterone derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040033999A1 true US20040033999A1 (en) | 2004-02-19 |
Family
ID=8233831
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/719,927 Expired - Fee Related US6437158B1 (en) | 1998-06-19 | 1999-06-14 | Testosterone derivative |
US10/177,989 Abandoned US20040033999A1 (en) | 1998-06-19 | 2002-06-21 | Testosterone derivative |
US10/964,076 Expired - Fee Related US6989378B2 (en) | 1998-06-19 | 2004-10-13 | Testosterone derivative |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/719,927 Expired - Fee Related US6437158B1 (en) | 1998-06-19 | 1999-06-14 | Testosterone derivative |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/964,076 Expired - Fee Related US6989378B2 (en) | 1998-06-19 | 2004-10-13 | Testosterone derivative |
Country Status (26)
Country | Link |
---|---|
US (3) | US6437158B1 (en) |
EP (1) | EP1087986B1 (en) |
JP (1) | JP2002518514A (en) |
KR (1) | KR100596649B1 (en) |
CN (1) | CN1172949C (en) |
AT (1) | ATE215961T1 (en) |
AU (1) | AU756739B2 (en) |
BR (1) | BR9911344A (en) |
CA (1) | CA2333985C (en) |
CZ (1) | CZ293319B6 (en) |
DE (1) | DE69901250T2 (en) |
DK (1) | DK1087986T3 (en) |
ES (1) | ES2175989T3 (en) |
HK (1) | HK1034263A1 (en) |
HU (1) | HUP0102274A3 (en) |
ID (1) | ID27260A (en) |
IL (1) | IL139689A (en) |
NO (1) | NO316518B1 (en) |
NZ (1) | NZ508299A (en) |
PL (1) | PL191285B1 (en) |
PT (1) | PT1087986E (en) |
RU (1) | RU2216546C2 (en) |
SK (1) | SK282796B6 (en) |
TR (1) | TR200003743T2 (en) |
WO (1) | WO1999067271A1 (en) |
ZA (1) | ZA200006813B (en) |
Cited By (1)
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EP1879382A2 (en) | 2006-07-10 | 2008-01-16 | Samsung Electronics Co., Ltd | Multi-screen display apparatus and method for digital broadcast receiver |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU5209600A (en) * | 1999-04-06 | 2000-10-23 | Akzo Nobel N.V. | Orally active androgens |
AU8201601A (en) * | 2000-07-28 | 2002-02-13 | Akzo Nobel Nv | 16alpha-methyl or ethyl substituted estrogens |
JP3774888B2 (en) * | 2001-11-28 | 2006-05-17 | 日本化薬株式会社 | Highly sensitive detection method for steroid compounds by LC-MS |
TW200400041A (en) * | 2002-05-30 | 2004-01-01 | Akzo Nobel Nv | Use of new etonogestrel esters |
TW200403065A (en) | 2002-05-30 | 2004-03-01 | Akzo Nobel Nv | New etonogestrel esters |
TW200404552A (en) * | 2002-05-30 | 2004-04-01 | Akzo Nobel Nv | Self administered contraception |
GB0304927D0 (en) | 2003-03-04 | 2003-04-09 | Resolution Chemicals Ltd | Process for the production of tibolone |
JO2505B1 (en) | 2003-03-14 | 2009-10-05 | باير شيرنغ فارما اكتنجيسيلشافت | method and pharmaceutical compositions for reliable achievements of acceptable serum testosterone levels |
JO2492B1 (en) | 2003-04-28 | 2009-10-05 | شيرينج ايه جي | pharmaceutical composition in the form of a hydrogel for transdermal administration of active ingredients |
PE20050677A1 (en) | 2003-12-22 | 2005-10-04 | Akzo Nobel Nv | STEROIDS WITH ANDROGENIC PROFILE AND MIXED PROGESTAGENIC |
UA89964C2 (en) | 2004-09-08 | 2010-03-25 | Н.В. Органон | 15beta-substituted steroids having selective estrogenic activity |
WO2008101030A1 (en) * | 2007-02-13 | 2008-08-21 | The Regents Of The University Of California | Methods for amplifying steroid hormone effects |
US20090018107A1 (en) * | 2007-07-13 | 2009-01-15 | Oral Delivery Technology Ltd. | Novel composition to increase muscle strength |
US20090017107A1 (en) * | 2007-07-13 | 2009-01-15 | Oral Delivery Technology Ltd. | Novel composition to increase libido |
US20100303937A1 (en) * | 2009-06-01 | 2010-12-02 | Michael Farber | Novel composition to increase testosterone levels |
CN102558267A (en) * | 2012-01-13 | 2012-07-11 | 宜城市共同药业有限公司 | Preparation method of testosterone enanthate |
KR20150011346A (en) | 2012-04-06 | 2015-01-30 | 안타레스 팔마, 인코퍼레이티드 | Needle assisted jet injection administration of testosterone compositions |
EP4349383A2 (en) | 2013-02-11 | 2024-04-10 | Antares Pharma, Inc. | Needle assisted jet injection device having reduced trigger force |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US5342834A (en) * | 1989-04-07 | 1994-08-30 | The Population Council, Inc. | Method for androgen supplementation |
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1999
- 1999-06-14 NZ NZ508299A patent/NZ508299A/en unknown
- 1999-06-14 BR BR9911344-9A patent/BR9911344A/en not_active Application Discontinuation
- 1999-06-14 EP EP99929208A patent/EP1087986B1/en not_active Expired - Lifetime
- 1999-06-14 ES ES99929208T patent/ES2175989T3/en not_active Expired - Lifetime
- 1999-06-14 CZ CZ20004779A patent/CZ293319B6/en not_active IP Right Cessation
- 1999-06-14 AU AU46101/99A patent/AU756739B2/en not_active Ceased
- 1999-06-14 KR KR1020007014182A patent/KR100596649B1/en not_active IP Right Cessation
- 1999-06-14 JP JP2000555922A patent/JP2002518514A/en active Pending
- 1999-06-14 PL PL344987A patent/PL191285B1/en not_active IP Right Cessation
- 1999-06-14 CN CNB998075175A patent/CN1172949C/en not_active Expired - Fee Related
- 1999-06-14 DE DE69901250T patent/DE69901250T2/en not_active Expired - Fee Related
- 1999-06-14 US US09/719,927 patent/US6437158B1/en not_active Expired - Fee Related
- 1999-06-14 SK SK1940-2000A patent/SK282796B6/en not_active IP Right Cessation
- 1999-06-14 ID IDW20002632A patent/ID27260A/en unknown
- 1999-06-14 RU RU2001101892/04A patent/RU2216546C2/en not_active IP Right Cessation
- 1999-06-14 CA CA002333985A patent/CA2333985C/en not_active Expired - Fee Related
- 1999-06-14 AT AT99929208T patent/ATE215961T1/en not_active IP Right Cessation
- 1999-06-14 PT PT99929208T patent/PT1087986E/en unknown
- 1999-06-14 IL IL13968999A patent/IL139689A/en not_active IP Right Cessation
- 1999-06-14 HU HU0102274A patent/HUP0102274A3/en unknown
- 1999-06-14 DK DK99929208T patent/DK1087986T3/en active
- 1999-06-14 TR TR2000/03743T patent/TR200003743T2/en unknown
- 1999-06-14 WO PCT/EP1999/004102 patent/WO1999067271A1/en active IP Right Grant
-
2000
- 2000-11-21 ZA ZA200006813A patent/ZA200006813B/en unknown
- 2000-12-18 NO NO20006455A patent/NO316518B1/en unknown
-
2001
- 2001-07-10 HK HK01104759A patent/HK1034263A1/en not_active IP Right Cessation
-
2002
- 2002-06-21 US US10/177,989 patent/US20040033999A1/en not_active Abandoned
-
2004
- 2004-10-13 US US10/964,076 patent/US6989378B2/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5342834A (en) * | 1989-04-07 | 1994-08-30 | The Population Council, Inc. | Method for androgen supplementation |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1879382A2 (en) | 2006-07-10 | 2008-01-16 | Samsung Electronics Co., Ltd | Multi-screen display apparatus and method for digital broadcast receiver |
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Owner name: AKZO NOBEL N.V., NETHERLANDS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LEYSEN, DIRK;VAN DER VOORT, HENDRIKUS A.A.;REEL/FRAME:013052/0119 Effective date: 20001106 |
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STCB | Information on status: application discontinuation |
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