Methods of making, using and pharmaceutical formulations comprising 7α, 11β-dimethyl-17β-hydroxyestra-4, 14-dien-3-one and 17 esters thereof

US 7,196,074 B2
Filed: 10/28/2002
Issued: 03/27/2007
Est. Priority Date: 03/31/2000
Status: Expired due to Term

First Claim

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1. A method for providing hormonal therapy to a patient comprising the oral administration of an androgen selected from the group consisting of 7α

,11β

-dimethyl-17β

hydroxyestra-4,14-dien-3-one, 17-ester of 7α

,11β

-dimethyl-17β

-hydroxyestra-4,14-dien-3-one, or mixtures thereof in an amount effective to provide hormonal therapy to a patient in need thereof, wherein the hormonal therapy is selected from the group consisting of hormone replacement therapy in males and females, male contraception, treatment of breast cancer, promotion and maintenance of muscle mass in a patient, treatment of osteoporosis, treatment of anemia, treatment for anabolic support, and hypergonadotropic conditions.

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Abstract

Methods of using 7α,11β-dimethyl-17β-hydroxyestra-4,14-dien-3-one (III)

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and 17 esters thereof for various hormonal therapies, oral and parenteral dosage forms comprising these actives, and processes for their preparation.

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96 Claims

1. A method for providing hormonal therapy to a patient comprising the oral administration of an androgen selected from the group consisting of 7α
- ,11β
  
  -dimethyl-17β
  
  hydroxyestra-4,14-dien-3-one, 17-ester of 7α
  
  ,11β
  
  -dimethyl-17β
  
  -hydroxyestra-4,14-dien-3-one, or mixtures thereof in an amount effective to provide hormonal therapy to a patient in need thereof, wherein the hormonal therapy is selected from the group consisting of hormone replacement therapy in males and females, male contraception, treatment of breast cancer, promotion and maintenance of muscle mass in a patient, treatment of osteoporosis, treatment of anemia, treatment for anabolic support, and hypergonadotropic conditions.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50)
- - 2. The method of claim 1, wherein an average dosage of about 1 mg to about 50 mg per day of the androgen is orally administered to the patient.
  - 3. The method of claim 2, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 4. The method of claim 1, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 5. The method of claim 4, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 6. The method of claim 5, wherein an average dosage of about 5 mg to about 40 mg per day of the androgen is orally administered to the patient.
  - 7. The method of claim 4, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 8. The method of claim 7, wherein an average dosage of about 5 mg to about 40 mg per day of the androgen is orally administered to the patient.
  - 9. The method of claim 2, wherein the oral administration is completed on a daily basis for at least one month.
  - 10. The method of claim 9, wherein the hormonal therapy continues at least 3 months.
  - 11. The method of claim 1, wherein the hormonal therapy is the treatment of hypogonadism in a male patient.
  - 12. The method of claim 11, wherein an average dosage of about 1 mg to about 50 mg per day of the androgen is orally administered to the patient.
  - 13. The method of claim 12, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 14. The method of claim 11, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 15. The method of claim 14, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 16. The method of claim 15, wherein an average dosage of about 5 mg to about 40 mg per day of the androgen is orally administered to the patient.
  - 17. The method of claim 14, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 18. The method of claim 17, wherein an average dosage of about 5 mg to about 40 mg per day of the androgen is orally administered to the patient.
  - 19. The method of claim 12, wherein the oral administration is completed on a daily basis for at least one month.
  - 20. The method of claim 19, wherein the hormonal therapy continues at least 3 months.
  - 21. The method of claim 1, wherein the hormonal therapy is male contraception.
  - 22. The method of claim 21, wherein an average dosage of about 1 mg to about 50 mg per day of the androgen is orally administered to the patient.
  - 23. The method of claim 22, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 24. The method of claim 21, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 25. The method of claim 24, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 26. The method of claim 25, wherein an average dosage of about 5 mg to about 40 mg per day of the androgen is orally administered to the patient.
  - 27. The method of claim 24, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 28. The method of claim 27, wherein an average dosage of about 5 mg to about 40 mg per day of the androgen is orally administered to the patient.
  - 29. The method of claim 22, wherein the oral administration is completed on a daily basis for at least one month.
  - 30. The method of claim 29, wherein the hormonal therapy continues at least 3 months.
  - 31. The method of claim 1, wherein the hormonal therapy is the promotion and maintenance of muscle mass in a patient.
  - 32. The method of claim 31, wherein the therapy continues for at least 3 months.
  - 33. The method of claim 31, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 34. The method of claim 31, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 35. The method of claim 34, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 36. The method of claim 34, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 37. The method of claim 1, wherein the hormonal therapy is the pilliative treatment of breast cancer.
  - 38. The method of claim 37, wherein the therapy continues for at least 3 months.
  - 39. The method of claim 37, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 40. The method of claim 37, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 41. The method of claim 40, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 42. The method of claim 40, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 43. The method of claim 1, wherein the hormonal therapy is hormone replacement therapy in females.
  - 44. The method of claim 43, further comprising the administration of estrogen.
  - 45. The method of claim 44, further comprising the administration of a progestin.
  - 46. The method of claim 44, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 47. The method of claim 44, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 48. The method of claim 47, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 49. The method of claim 47, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 50. The method of claim 1, wherein the androgen is administered as a formulation comprising the androgen and a pharmaceutically-acceptable oily carrier.

51. A method for providing hormonal therapy to a patient comprising administering parenterally to the patient an androgen selected from the group consisting of 7α
- ,11β
  
  -dimethyl-17β
  
  -hydroxyestra-4,14-dien-3-one, a 17-ester of 7α
  
  ,11β
  
  -dimethyl-17β
  
  -hydroxyestra-4,14-dien-3-one, and mixtures thereof in an amount effective to provide hormonal therapy to the patient, wherein the hormonal therapy is selected from the group consisting of hormone replacement therapy in males and females, male contraception, treatment of breast cancer, promotion and maintenance of muscle mass in a patient, treatment of osteoporosis, treatment of anemia, treatment for anabolic support, and hypergonadotropic conditions.
- View Dependent Claims (52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96)
- - 52. The method of claim 51, wherein an average dosage of about 1 to about 400 mg of the androgen is parenterally administered to the patient.
  - 53. The method of claim 52, wherein the androgen is administered to the patient about once every month.
  - 54. The method of claim 53, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 55. The method of claim 51, wherein the androgen is administered to the patient about once every two to four months.
  - 56. The method of claim 55, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 57. The method of claim 56, wherein an average dosage of about 1 to about 400 mg of the androgen is parenterally administered to the patient.
  - 58. The method of claim 54, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 59. The method of claim 54, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 60. The method of claim 51, wherein the average amount of the androgen administered during the period of hormonal therapy is from about 1 to about 40 mg per week.
  - 61. The method of claim 51, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate and is administered as a formulation comprising 7α
      
      ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate and a pharmaceutically-acceptable aqueous carrier.
  - 62. The method of claim 61, wherein the 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate is crystalline and the formulation comprises a suspension of 7α
      
      ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate in the pharmaceutically-acceptable aqueous carrier.
  - 63. The method of claim 62, wherein the formulation is administered about once every month.
  - 64. The method of claim 62, wherein the formulation is administered about once every two to four months.
  - 65. The method of claim 64, wherein from about 100 mg to about 400 mg of the androgen is administered to the patient.
  - 66. The method of claim 51, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one and is administered as a formulation comprising 7α
      
      ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one and a pharmaceutically-acceptable aqueous carrier.
  - 67. The method of claim 66, wherein the 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one is crystalline and the formulation comprises a suspension of 7α
      
      ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one in the pharmaceutically-acceptable aqueous carrier.
  - 68. The method of claim 67, wherein the formulation is administered about once every month.
  - 69. The method of claim 67, wherein the formulation is administered about once every two to four months.
  - 70. The method of claim 69, wherein from about 100 mg to about 400 mg of the androgen is administered to the patient.
  - 71. The method of claim 51, wherein the hormonal treatment is the treatment of hypogonadism in male patients.
  - 72. The method of claim 71, wherein an average dosage of about 1 to about 400 mg of the androgen is parenterally administered to the patient.
  - 73. The method of claim 72, wherein the androgen is administered to the patient about once every month.
  - 74. The method of claim 71, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 75. The method of claim 71, wherein the androgen is administered to the patient about once every two to four months.
  - 76. The method of claim 75, wherein an average dosage of about 1 to about 400 mg of the androgen is parenterally administered to the patient.
  - 77. The method of claim 74, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 78. The method of claim 74, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 79. The method of claim 71, wherein the average amount of the androgen administered during the period of hormonal therapy is from about 1 to about 40 mg per week.
  - 80. The method of claim 71, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate and is administered as a formulation comprising 7α
      
      ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate and a pharmaceutically-acceptable aqueous carrier.
  - 81. The method of claim 80, wherein the 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate is crystalline and the formulation comprises a suspension of 7α
      
      ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate in the pharmaceutically-acceptable aqueous carrier.
  - 82. The method of claim 81, wherein the formulation is administered about once every month.
  - 83. The method of claim 81, wherein the formulation is administered about once every two to four months.
  - 84. The method of claim 81, wherein from about 100 mg to about 400 mg of the androgen is administered to the patient.
  - 85. The method of claim 51, wherein the hormonal treatment is male contraception.
  - 86. The method of claim 85, wherein an average dosage of about 1 to about 400 mg of the androgen is parenterally administered to the patient.
  - 87. The method of claim 86, wherein the androgen is administered to the patient about once every month.
  - 88. The method of claim 85, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.
  - 89. The method of claim 85, wherein the androgen is administered to the patient about once every two to four months.
  - 90. The method of claim 88, wherein an average dosage of about 1 to about 400 mg of the androgen is parenterally administered to the patient.
  - 91. The method of claim 88, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate.
  - 92. The method of claim 88, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one 17-undecanoate.
  - 93. The method of claim 85, wherein the average amount of the androgen administered during the period of hormonal therapy is from about 1 to about 40 mg per week.
  - 94. The method of claim 85, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate and is administered as a formulation comprising 7α
      
      ,11β
      
      -dimethyl-17β
      
      hydroxyestra-4,14-dien-3-one 17β
      
      -4-trans-n-butylcyclohexanecarboxylate and a pharmaceutically-acceptable aqueous carrier.
  - 95. The method of claim 85, wherein the androgen is 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one and is administered as a formulation comprising 7α
      
      ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one and a pharmaceutically-acceptable aqueous carrier.
  - 96. The method of claim 93, wherein the androgen is a 17-ester of 7α
    - ,11β
      
      -dimethyl-17β
      
      -hydroxyestra-4,14-dien-3-one.

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Current Assignee
Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services
Original Assignee
United States Department Of Health And Human Services (Government of the United States of America)
Inventors
Blye, Richard P., Kim, Hyun K., Acosta, Carmie Kirk, Rao, Pemmaraju Narasimha
Primary Examiner(s)
QAZI, SABIHA NAIM

Application Number

US10/281,794
Publication Number

US 20030130243A1
Time in Patent Office

1,611 Days
Field of Search

514/167, 514/169, 514/170, 514/182, 514/179, 552/647
US Class Current

514/178
CPC Class Codes

A61P 15/00   Drugs for genital or sexual...

A61P 15/10   for impotence

A61P 15/16   Masculine contraceptives

A61P 21/06   Anabolic agents androgens A...

A61P 5/26   Androgens

A61P 5/30   Oestrogens

C07J 1/00   Normal steroids containing ...

C07J 1/0059   substituted in position 17 ...

C07J 1/007   the substituent being an OH...

C07J 1/0074   Esters

C07J 21/006   at position 3

C07J 71/001   Oxiranes

Methods of making, using and pharmaceutical formulations comprising 7α, 11β-dimethyl-17β-hydroxyestra-4, 14-dien-3-one and 17 esters thereof

First Claim

2 Assignments

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Abstract

57 Citations

96 Claims

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Methods of making, using and pharmaceutical formulations comprising 7α, 11β-dimethyl-17β-hydroxyestra-4, 14-dien-3-one and 17 esters thereof

First Claim

2 Assignments

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0 Petitions

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Accused Products

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Abstract

57 Citations

96 Claims

Specification

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