Ganglioside derivatives

• US 4,728,641 A
• Filed: 07/18/1984
• Issued: 03/01/1988
• Est. Priority Date: 07/21/1983
• Status: Expired due to Fees

• Current Assignee: Burroughs Wellcome Company Research Triangle Park State of North Carolina 27709
• Original Assignee: Burroughs Wellcome and Co.
• Inventors: Cavallo, Giovanni, Tubaro, Ezio
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US06/632,200
• Time in Patent Office: 1,322 Days
• Field of Search: 536/55.1, 536/55.3, 536/123, 536/53, 514/54
• US Class Current: 514/54
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 15/10 containing unsaturated carbon-to-carbon bonds
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A novel mono-sialo ganglioside derivative substantially identical chemically and physically with a product prepared by

(a) concentration of an aqueous solution of a mono-sialo ganglioside and calcium ions under sub-atmospheric pressure at 40°-80° C. for 18-240 hours,

(b) adjustment of the pH to 2-3, followed by dialysis, and

(c) evaporation of the aqueous solvent.

The novel ganglioside is believed to be a new physical form of the known ganglioside G_M1 and shows activity against bacteria, viruses, protozoal, fungi and tumors. It has previously been suggested that gangliosides in general may be useful in the treatment of neurological disorders but not that they affect the activity of phagocytes.

Claims

1. A method of treating bacterial infections in a mammal comprising administering to a mammal an effective antibacterial amount of a ganglioside G_M1 P compound characterised in that:

(a) by thin layer chromatography

(i) it gives a positive reaction to sulphuric acid reagent (concentrated sulphuric acid;

water, 1;

1), resorcinol reagent, orcinol/FeCl₃ and other typical reagents for ganglioside detection,

(ii) it gives litte reaction to ninhydrin reagent (0.2% ninhydrin in ethanol),

(b) it has, when in aqueous solution, a ¹³ C n.m.r. spectrum substantially identical to that shown in FIG. 2,

(c) it has in vivo activity in mice against klebsiella pneumoniae, and

(d) It has in vivo activity in mice against Herpes HSV-1 (strain F) to said mammal.

2. A method of treating fungal infections in a mammal comprising administering to a mammal an effective antifungal amount of a ganglioside G_M1 P compound characterised in that:

(a) by thin layer chromatography

(i) it gives a positive reaction to sulphuric acid reagent (concentrated sulphuric acid;

water, 1;

1), resorcinol reagent, orcinol/FeCl₃ and other typical reagents for ganglioside detection,

(ii) it gives little reaction to ninhydrin reagent (0.2% ninhydrin in ethanol),

(b) it has, when in aqueous solution, a ¹³ C n.m.r. spectrum substantially identical to that shown in FIG. 2,

(c) it has in vivo activity in mice against klebsiella pneumoniae, and

(d) it has in vivo activity in mice aganst Herpes HSV-1 (strain F) to said mammal.

3. A method of treating protozoal infections in a mammal comprising administering to a mammal an effective antiprotozoal amount of a ganglioside G_M1 P compound characterised in that:

(a) by thin layer chromatography

(i) it gives a positive reaction ot sulphuric acid reagent (concentrated sulphuric acid;

water, 1;

1), resorcinol reagent, orcinol,FeCl₃ and other typical reagents for ganglioside detection,

(ii) it gives little reaction to ninhydrin reagent (0.2% ninhydrin in ethanol),

(b) it has, when in aqueous solution, a ¹³ C n.m.r. spectrum substantially identical to that shown in FIG. 2,

(c) it has in vivo activity in mice against klebsiella pneumoniae, and

(d) It has in vivo activity in mice against Herpes HSV-1 (strain F) to said mammal.

4. A method of treating viral infections in a mammal comprising administering to a mammal an effective antiviral amount of a ganglioside G_M1 P compound characterised in that:

(a) by thin layer chromatography

(i) it gives a positive reaction to sulphuric acid reagent (concentrated sulphuric acid;

water, 1;

1), resorcinol reagent, orcinol/FeCl₃ and other typical reagents for ganglioside detection,

(ii) it gives little reaction to ninhydrin reagent (0.2% ninhydrin in ethanol),

(b) it has, when in aqueous solution, a ¹³ C n.m.r. spectrum substantially identical to that shown in FIG. 2,

(c) it has in vivo activity in mice against klebsiella pneumoniae, and

(d) It has in vivo activity in mice against Herpes HSV-1 (strain F).