التفاصيل البيبلوغرافية
| العنوان: |
Patient populations and treatment methods |
| Document Number: |
20100075937 |
| تاريخ النشر: |
March 25, 2010 |
| Appl. No: |
12/566565 |
| Application Filed: |
September 24, 2009 |
| مستخلص: |
The invention provides, inter alia, methods to treat, e.g., hyperglycemia or diabetes patients having two or more of a BMI of at least 28 or 29, a fasting insulin level of at least 4 μU/mL or at least 6 μU/mL and optionally (i) a serum MCP1 level of at least about 400 pg/mL or at least about 500 pg/mL. The treatment method includes administering 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol and optionally another compound such as metformin or glyburide. Specific embodiments include use of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol for the treatment of hypercholesterolemia in a patient and a BMI of at least 28 or 29 and optionally hyperglycemia. In these embodiments, the patient will most preferably have a fasting insulin level of at least 4 μU/mL or at least 5 μU/mL. |
| Inventors: |
Flores-Riveros, Jaime (Thousands Oaks, CA, US); Frincke, James M. (San Diego, CA, US); Reading, Christopher L. (San Diego, CA, US); Stickney, Dwight (Granite Bay, CA, US) |
| Assignees: |
Hollis-Eden Pharmaceuticals, Inc. (San Diego, CA, US) |
| Claim: |
1. A method to treat a patient(s) having diabetes, hyperglycemia, a macrovascular disease, a microvascular disease, nonalcoholic steatohepatitis, acute alcoholic hepatitis or a dyslipidemia condition, comprising, (a) determining the body mass index (BMI) of the patient(s); (b) in a patient(s) of step (a) having a BMI of at least about 28, determining the level of fasting blood insulin; (c) selecting patient(s) with a fasting blood insulin level of at least about 4 μU/mL as patient(s) for treatment and/or a fasting blood C peptide level of at least about 2 ng/mL; and (d) treating the patient(s) of step (c) with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol, 17α-ethynylandrost-5-ene-3β, 7β, 16α, 17β-tetrol, 17α-ethynylandrost-5-ene-3α,7β,16α, 17β-tetrol, androst-5-ene-3β, 7β, 16α, 17β-tetrol or androst-5-ene-3α,7β,16α, 17β-tetrol. |
| Claim: |
2. The method of claim 1 wherein the method further comprises determining the blood or serum level of MCP1 and selecting a patient(s) having a MCP1 level of at least about 400 pg/mL and a fasting blood insulin level of at least about 4 μU/mL as patient(s) for treatment according to step (d). |
| Claim: |
3. The method of claim 2 wherein the patient(s) has a BMI of at least 29. |
| Claim: |
4. The method of claim 2 wherein, (a) the patient(s) has type 2 diabetes and the patient(s) is treated with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; (b) the patient(s) has type 1 diabetes and the patient(s) is treated with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; or (c) the patient(s) has pre-diabetic hyperglycemia and the patient(s) is treated with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol. |
| Claim: |
5. The method of claim 2 wherein, (a) the patient(s) has a microvascular disease and optionally hyperglycemia, wherein the microvascular disease optionally is retinopathy, neuropathy or nephropathy, and the patient(s) is treated with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; (b) the patient(s) has a macrovascular disease and optionally hyperglycemia, wherein the macrovascular disease optionally is atherosclerosis, arteriosclerosis, a stroke, hypertension or a myocardial infarction, and the patient(s) is treated with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; (c) the patient(s) has a dyslipidemia condition and optionally hyperglycemia, wherein the dyslipidemia condition is hypercholesterolemia or hypertriglyceridemia, and the patient(s) is treated with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; or (d) the patient(s) has nonalcoholic steatohepatitis or acute alcoholic hepatitis and optionally hyperglycemia, and the patient(s) is treated with an effective amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol. |
| Claim: |
6. Use of a compound for the preparation of a medicament for the treatment of diabetes, hyperglycemia, macrovascular disease, microvascular disease, nonalcoholic steatohepatitis or acute alcoholic hepatitis or a hyperlipidemia condition in patient(s) having (i) a BMI of at least about 28, and (ii) a fasting blood insulin level of at least about 4 μU/mL and/or a fasting blood C peptide level of at least about 2 ng/mL, wherein the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol, 17α-ethynylandrost-5-ene-3β, 7β, 16α, 17β-tetrol, 17α-ethynylandrost-5-ene-3α,7β,16α, 17β-tetrol, androst-5-ene-3β, 7β, 16α, 17β-tetrol or androst-5-ene-3α,7β,16α, 17β-tetrol. |
| Claim: |
7. Use according to claim 6 wherein the patient(s) has (i) a blood serum MCP1 level of at least about 400 pg/mL and a fasting blood insulin level of at least about 4 μU/mL, (ii) a BMI of at least about 29 or (iii) a blood serum MCP1 level of at least about 400 pg/mL, a fasting blood insulin level of at least about 4 μU/mL and a BMI of at least about 29. |
| Claim: |
8. Use according to claim 7 wherein, (a) the compound is for the treatment of type 2 diabetes and the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; (b) the compound is for the treatment of type 1 diabetes and the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; or (c) the compound is for the treatment of pre-diabetic hyperglycemia and the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol. |
| Claim: |
9. Use according to claim 7 wherein, (a) the compound is for the treatment of a microvascular disease, wherein the microvascular disease optionally is retinopathy, neuropathy or nephropathy, and the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; (b) the compound is for the treatment of a macrovascular disease, wherein the macrovascular disease optionally is atherosclerosis, atherosclerosis, a stroke, hypertension or a myocardial infarction, and the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; (c) the compound is for the treatment of a dyslipidemia condition, wherein the dyslipidemia condition is hypercholesterolemia or hypertriglyceridemia, and the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol; or (d) the compound is for the treatment of nonalcoholic steatohepatitis and the compound is 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol. |
| Claim: |
10. A method to treat hyperglycemia, diabetes, dyslipidemia, a macrovascular disease, a microvascular disease, nonalcoholic steatohepatitis or acute alcoholic hepatitis in a patient(s) in need thereof comprising administering an amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol sufficient to maintain a serum level of about 0.5 ng/mL to about 200 ng/mL for about 2 hours to at least about 4 hours. |
| Claim: |
11. The method of claim 10 wherein the amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol is sufficient to maintain a serum level of about 3 ng/mL to about 50 ng/mL for about 2 hours to at least about 4 hours. |
| Claim: |
12. The method of claim 11 wherein about 4 mg to about 200 mg of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol in the form of a dose for oral administration that is administered each day as a single dose or twice as two doses containing about 2 mg per dose to about 100 mg per dose. |
| Claim: |
13. The method of claim 11 wherein about 10 mg to about 100 mg of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol is administered in the form of a unit dose for oral administration, optionally wherein the 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol is administered each day as a single dose or twice as two doses containing about 5 mg per dose to about 50 mg per dose. |
| Claim: |
14. The method of claim 11 wherein the patient(s) has a BMI of at least about 28, has (i) a fasting blood insulin level of at least about 4 μU/mL and/or (ii) a fasting blood C peptide level of at least about 2 ng/mL, and optionally a blood level of MCP1 of at least about 400 pg/mL. |
| Claim: |
15. The method of claim 11 wherein, (a) the patient(s) has type 2 diabetes; (b) the patient(s) has type 1 diabetes; or (c) the patient(s) has pre-diabetic hyperglycemia. |
| Claim: |
16. The method of claim 11 wherein, (a) the patient(s) has a microvascular disease and optionally hyperglycemia, wherein the microvascular disease optionally is retinopathy, neuropathy or nephropathy; (b) the patient(s) has a macrovascular disease and optionally hyperglycemia, wherein the macrovascular disease optionally is atherosclerosis, arteriosclerosis, hypertension, a thromboembolism, a stroke or a myocardial infarction; (c) the patient(s) has a dyslipidemia condition and optionally hyperglycemia, wherein the dyslipidemia condition optionally is hypercholesterolemia or hypertriglyceridemia; or (d) the patient(s) has nonalcoholic steatohepatitis and optionally hyperglycemia. |
| Claim: |
17. A pharmaceutical formulation for oral administration comprising one or more excipients and 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol in an amount sufficient to maintain a serum level in a patient of about 0.5 ng/mL to about 200 ng/mL for about 2 hours to at least about 4 hours. |
| Claim: |
18. The pharmaceutical formulation of claim 17 wherein the amount of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol is sufficient to maintain a blood level of about 3 ng/mL to about 50 ng/mL for about 2 hours to at least about 4 hours. |
| Claim: |
19. The pharmaceutical formulation of claim 18 wherein the pharmaceutical formulation is a unit dosage for oral administration wherein each unit dosage contains about 2 mg, about 5 mg, about, 10 mg, about 25 mg, about 50 mg or about 100 mg of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol. |
| Claim: |
20. The pharmaceutical formulation of claim 18 wherein the pharmaceutical formulation is a unit dosage for oral administration wherein each unit dosage contains about 15 mg, about 30 mg, about 45 mg, about 60 mg or about 90 mg of 17α-ethynylandrost-5-ene-3β, 7β, 17β-triol. |
| Current U.S. Class: |
514/182 |
| Current International Class: |
61; 61; 61; 61; 61; 07 |
| رقم الانضمام: |
edspap.20100075937 |
| قاعدة البيانات: |
USPTO Patent Applications |