Treatment of renal disorders, diabetic nephropathy and dyslipidemias

• US 20070238788A1
• Filed: 12/22/2006
• Published: 10/11/2007
• Est. Priority Date: 12/22/2005
• Status: Active Grant

• Current Assignee: Kiacta Sarl
• Original Assignee: Kiacta Sarl
• Inventors: Hauck, Wendy, Hamet, Pavel
• Granted Patent: US 8,372,886 B2
• Time in Patent Office: Days
• US Class Current: 514/578
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

Disclosed herein are methods, compounds and compositions for preventing or treating a renal disorder or chronic kidney diseases, including nephropathies such as diabetic nephropathy. The invention generally includes administering to a subject 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof, e.g., 1,3-propanedisulfonic acid sodium salt. The invention also relates to methods, compounds and compositions for the prevention and/or treatment of for preventing or treating a renal disorder complication. The invention further relates to methods, compounds and compositions for the prevention and/or treatment of dyslipidemia, and more particularly for reducing levels of harmful serum lipid levels, especially cholesterol and triglycerides in diabetic patients.

Claims

1. A method for preventing or treating a renal disorder in a subject in need thereof, comprising administering to said subject an effective amount of a compound of the Formula (I):

Y—

(CH₂)_n—

(CH)_t—

[CH₂Y]_m 

 

(I)

wherein Y is SO₃X or OSO₃X independently chosen for each occurrence;

X is a cationic group which independently for each occurrence is hydrogen, lithium, sodium, potassium, calcium, magnesium, trialkylammonium or aluminum;

n is 1, 2, 3 or 4;

t is 0 when m is 1; and

t is 1 when m is 2;

wherein said subject does not have amyloidosis.

2. The method of claim 1, wherein said compound is 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof.

3. The method of claim 1, wherein said compound is 1,3-propanedisulfonic acid sodium salt.

4. The method of claim 1 wherein the renal disorder is nephropathy.

5. The method of claim 4, wherein the nephropathy is diabetic nephropathy, hypertensive nephropathy, analgesic nephropathy, IgA-nephropathy, ischemic nephropathy, HIV-associated nephropathy, membranous nephropathy, glomerulosclerosis, radiocontrast media-induced nephropathy, toxic nephropathy, analgesic-induced nephrotoxicity or cisplatin nephropathy.

7. The method of claim 1, wherein clearance of creatinine and/or clearance of uric acid is improved in the subject subsequent to said administration.

6. The method of 5, wherein the nephropathy is diabetic nephropathy.

8. A method for preventing or treating a renal disorder complication in a subject in need thereof comprising administering to said subject an effective amount of a compound of the Formula (I):

Y—

(CH₂)_n—

(CH)_t—

[CH₂Y]_m 

 

(I)

wherein Y is SO₃X or OSO₃X independently chosen for each occurrence;

X is a cationic group which independently for each occurrence is hydrogen, lithium, sodium, potassium, calcium, magnesium, trialkylammonium or aluminum;

n is 1, 2, 3 or 4;

t is 0 when m is 1; and

t is 1 when m is 2;

wherein said subject does not have amyloidosis.

9. The method of claim 8, wherein said compound is 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof.

10. The method of claim 8, wherein said compound is 1,3-propanedisulfonic acid sodium salt.

11. The method of claim 8, wherein the renal disorder complication is a vascular disease, cardiovascular disease, hyperlipidemia, diabetic dyslipidemia, metabolic syndrome, obesity, anemia, oedema or pancreatitis.

12. The method of claim 11, wherein the hyperlipidemia is hypercholesterolemia or hypertriglyceridemia.

13. The method of claim 11, wherein the vascular and cardiovascular disease is hypertension, arteriosclerosis, atherosclerosis, coronary artery disease, and/or congestive heart failure.

14. The method of claim 11, wherein the cardiovascular disease complications is/are macrovascular complications, microvascular complications, coronary heart disease, atherosclerosis, stroke, angina and/or hypertension.

15. The method of claim 8, wherein clearance of creatinine and/or clearance of uric acid is improved in the subject subsequent to said administration.

16. A method for the prevention or treatment of dyslipidemia in a subject in need thereof, comprising administering to said subject an effective amount of a compound of the Formula (I):

Y—

(CH₂)_n—

(CH)_t—

[CH₂Y]_m 

 

(I)

wherein Y is SO₃X or OSO₃X independently chosen for each occurrence;

X is a cationic group which independently for each occurrence is hydrogen, lithium, sodium, potassium, calcium, magnesium, trialkylammonium or aluminum;

n is 1, 2, 3 or 4;

t is 0 when m is 1; and

t is 1 when m is 2.

17. The method of claim 16, wherein the dyslipidemia is hyperlipidemia.

18. The method of claim 16, wherein said compound is 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof.

19. The method of claim 16, wherein said compound is 1,3-propanedisulfonic acid sodium salt.

20. The method of claim 17, wherein the hyperlipidemia is associated with undesirably high levels of circulating blood lipids and/or lipoproteins which is a triglyceride, cholesterol, ApoB, LpA, high-density lipoprotein cholesterol (HDLC), very low density lipoprotein cholesterol (VLDLC), low density lipoprotein cholesterol (LDLC), intermediate density lipoprotein cholesterol or a free fatty acid.

21. The method of claim 20, wherein any one of said circulating blood lipids and/or lipoproteins is reduced in the subject.

22. A method of reducing serum lipid levels in a subject in need thereof comprising administering to said subject an effective amount of a compound of the Formula (I):

Y—

(CH₂)_n—

(CH)_t—

[CH₂Y]_m 

 

(I)

wherein Y is SO₃X or OSO₃X independently chosen for each occurrence;

X is a cationic group which independently for each occurrence is hydrogen, lithium, sodium, potassium, calcium, magnesium, trialkylammonium or aluminum;

n is 1, 2, 3 or 4;

t is 0 when m is 1; and

t is 1 when m is 2.

23. The method of claim 22, wherein the serum lipids are triglycerides

24. The method of claim 22, wherein the subject is suffering from or at risk of suffering from arteriosclerosis, atherosclerosis, coronary artery disease, congestive heart failure, hypertriglyceridemia, hyperlipidemia, hypercholesterolemia, diabetic dyslipidemia, metabolic syndrome and/or obesity.

25. The method of claim 22, wherein said compound is 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof.

26. The method of claim 22, wherein said compound is 1,3-propanedisulfonic acid sodium salt.

27. A method of increasing creatinine clearance in a subject in need thereof comprising administering to said subject an effective amount of a compound of the Formula (I)

Y—

(CH₂)_n—

(CH)_t—

[CH₂Y]_m 

 

(I)

wherein Y is SO₃X or OSO₃X independently chosen for each occurrence;

X is a cationic group which independently for each occurrence is hydrogen, lithium, sodium, potassium, calcium, magnesium, trialkylammonium or aluminum;

n is 1, 2, 3 or 4;

t is 0 when m is 1; and

t is 1 when m is 2;

wherein said subject does not have amyloidosis.

28. A method of decreasing serum uric acid levels in a subject in need thereof comprising administering to said subject an effective amount of a compound of the Formula (I):

Y—

(CH₂)_n—

(CH)_t—

[CH₂Y]_m 

 

(I)

wherein Y is SO₃X or OSO₃X independently chosen for each occurrence;

X is a cationic group which independently for each occurrence is hydrogen, lithium, sodium, potassium, calcium, magnesium, trialkylammonium or aluminum;

n is 1, 2, 3 or 4;

t is 0 when m is 1; and

t is 1 when m is 2;

wherein said subject does not have amyloidosis.

29. A method for improving kidney function in a human subject in need thereof, comprising administering to said subject an effective amount of a compound of the Formula (I):

Y—

(CH₂)_n—

(CH)_t—

[CH₂Y]_m 

 

(I)

wherein Y is SO₃X or OSO₃X independently chosen for each occurrence;

X is a cationic group which independently for each occurrence is hydrogen, lithium, sodium, potassium, calcium, magnesium, trialklammonium or aluminum;

n is 1, 2, 3 or 4;

t is 0 when m is 1; and

t is 1 when m is 2;

wherein said subject does not have amyloidosis.

30. The method of claim 29, wherein said method positively affects in said subject a kidney function parameter which is albuminuria, proteinurea, creatinine clearance or urea clearance.

31. The method of 30, wherein said kidney function is assessed using an assay which measures serum creatinine level, creatinine clearance rate, cystatin C clearance rate, 24-hour urinary creatinine clearance, 24-hour urinary protein secretion, glomerular filtration rate, urinary albumin creatinine ratio, albumin excretion rate or renal biopsy.

32. A method for preventing diabetic nephropathy in a subject in need therefore, comprising administering to said subject 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof, wherein said subject does not have amyloidosis.