GALACTOSE-PRONGED POLYSACCHARIDES IN A FORMULATION FOR ANTIFIBROTIC THERAPIES

• US 20080107622A1
• Filed: 11/13/2007
• Published: 05/08/2008
• Est. Priority Date: 05/16/2006
• Status: Active Grant

• Current Assignee: Galectin Therapeutics Inc
• Original Assignee: Galectin Therapeutics Inc
• Inventors: Zomer, Eliezer, Klyosov, Anatole, Platt, David
• Granted Patent: US 8,236,780 B2
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/732 Pectin
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C08B 37/0045 alpha-D-Galacturonans, e.g. methyl ester of (alpha-1,4)-linked D-galacturonic acid units, i.e. pectin, or hydrolysis product of methyl ester of alpha-1,4-linked D-galacturonic acid units, i.e. pectinic acid; Derivatives thereof
• CPC Class Codes: C08B 37/006 Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof

Abstract

Methods and compositions for reducing fibrosis and cirrhosis are provided in which an effective dose of an admixture of a polysaccharide compound and, for example, a compound selected from the group consisting of antibodies specific to intracellular or cell-surface: (i) beta-PDGF receptors; (ii) synaptophysin; (iii) zvegf3; (iv) CCR1 receptors; (v) connective tissue growth factor; (vi) alpha 1-smooth muscle actin; (vii) matrix metalloproteinases MMP 2 and MMP9; (viii) matrix metalloproteinase inhibitors TIMP1 and TMP2; (ix) integrins; (x) TFG-β1; (xi) endothelin receptor antagonists; and (xii) collagen synthesis and degradation modulating compounds; (xiii) actin synthesis and degradation modulating compounds; and (xiv) tyrosine kinases is administered to an animal in order to treat fibrosis.

Claims

1. A method comprising the steps of:

Obtaining an admixture of a polysaccharide compound and a compound selected from the group consisting of antibodies specific to cell-surface and/or intracellular;

(i) beta-PDGF receptors;

(ii) synaptophysin;

(iii) zvegf3;

(iv) CCR1 receptors;

(v) connective tissue growth factor;

(vi) alpha 1-smooth muscle actin;

(vii) matrix metalloproteinases MMP 2 and MMP9;

(viii) matrix metalloproteinase inhibitors TIMP1 and TMP2;

(ix) integrins;

(x) TFG-β

1;

(xi) endothelin receptor antagonists; and

(xii) collagen synthesis and degradation modulating compounds;

(xiii) actin synthesis and degradation modulating compounds; and

(xiv) tyrosine kinases; and

Administering to a mammal an effective dose of the admixture to treat fibrosis.

2. A method according to claim 1, wherein the polysaccharide compound is a galactomannan or galactomannan derivative.

3. A method according to claim 1, where the polysaccharide compound is a galacto-rhamnogalacturonan or galacto-rhamnogalacturonan derivative.

4. A method according to claim 1, where the polysaccharide compound is a galacto-arabinogalactan or galcacto-arabinogalactan derivative.

5. A method comprising the steps of:

Obtaining an admixture of a polysaccharide compound and a compound selected from the group consisting of;

(i) IL-1;

(ii) IL-10;

(iii) anti-zvegf3 compounds;

(iv) interferon alpha G (alpha

     5);

(v) hepatic stellate cell activation inhibiting compounds; and

Administering to a mammal an effective dose of the admixture to treat fibrosis.

6. A method according to claim 5, wherein the polysaccharide compound is a galactomannan or galactomannan derivative.

7. A method according to claim 5, where the polysaccharide compound is a galacto-rhamnogalacturonan or galacto-rhamnogalacturonan derivative.

8. A method according to claim 5, where the polysaccharide compound is a galacto-arabinogalactan or galcacto-arabinogalactan derivative.

9. A method comprising the steps of:

Obtaining an admixture of a polysaccharide compound and a compound selected from the group consisting of;

(i) Vitamin E;

(ii) alpha-lipoic acid;

(iii) Tetrandrine;

(iv) Silymarin and Silymarin derivatives; and

(v) Thalidomide and Thalidomide analogs; and

Administering to a mammal an effective dose of the admixture to treat fibrosis.

10. A method according to claim 9, wherein the polysaccharide compound is a galactomannan or galactomannan derivative.

11. A method according to claim 9, where the polysaccharide compound is a galacto-rhamnogalacturonan or galacto-rhamnogalacturonan derivative.

12. A method according to claim 9, where the polysaccharide compound is a galacto-arabinogalactan or galcacto-arabinogalactan derivative.

13. A method comprising the steps of:

Obtaining an admixture of a polysaccharide compound and a compound selected from the group consisting of;

(i) cysteine;

(ii) L-cysteine;

(iii) L-methionine;

(iv) S-adenosyl methionine;

(v) S-methyl cysteine; and

(vi) N-acetyl cysteine; and

Administering to a mammal an effective dose of the admixture to treat fibrosis.

14. A method according to claim 13, wherein the polysaccharide compound is a galactomannan or galactomannan derivative.

15. A method according to claim 13, where the polysaccharide compound is a galacto-rhamnogalacturonan or galacto-rhamnogalacturonan derivative.

16. A method according to claim 13, where the polysaccharide compound is a galacto-arabinogalactan or galcacto-arabinogalactan derivative.

17. A method comprising the steps of:

Obtaining an admixture of a polysaccharide compound and a compound selected from the group consisting of;

(i) copper chelating compounds;

(ii) halofuginone;

(iii) β

-amino-propionitriles;

(iv) Type V cyclic nucleotide phosphodiesterase inhibitors;

(v) antiviral compounds;

(vi) alcohol abstinence compounds; and

(vii) herbal compounds; and

Administering to a mammal an effective dose of the admixture to treat fibrosis.

18. A method according to claim 17, wherein the polysaccharide compound is a galactomannan or galactomannan derivative.

19. A method according to claim 17, where the polysaccharide compound is a galacto-rhamnogalacturonan or galacto-rhamnogalacturonan derivative.

20. A method according to claim 17, where the polysaccharide compound is a galacto-arabinogalactan or galcacto-arabinogalactan derivative.

21. A method comprising the steps of:

Obtaining an admixture of a polysaccharide compound and a compound selected from the group consisting of;

(i) dextran sulfate;

(ii) pentosan polysulfate;

(iii) chondroitin sulfate;

(iv) heparin sulfate; and

(v) heparin; and

Administering to a mammal an effective dose of the admixture to treat fibrosis.

22. A method according to claim 21, wherein the polysaccharide compound is a galactomannan or galactomannan derivative.

23. A method according to claim 21, where the polysaccharide compound is a galacto-rhamnogalacturonan or galacto-rhamnogalacturonan derivative.

24. A method according to claim 21, where the polysaccharide compound is a galacto-arabinogalactan or galcacto-arabinogalactan derivative.

25. A method comprising the steps of:

Obtaining an admixture of a polysaccharide compound and a compound selected from the group consisting of;

(i) corticosteroids;

(ii) colchicine;

(iii) tranilast;

(iv) captopril;

(v) malotilate; and

(vi) aspirin; and

(vii) hepatic inflammation inhibiting compounds; and

Administering to a mammal an effective dose of the admixture to treat fibrosis.

26. A method according to claim 25, wherein the polysaccharide compound is a galactomannan or galactomannan derivative.

27. A method according to claim 25, where the polysaccharide compound is a galacto-rhamnogalacturonan or galacto-rhamnogalacturonan derivative.

28. A method according to claim 25, where the polysaccharide compound is a galacto-arabinogalactan or galcacto-arabinogalactan derivative.