Antitumor and anticholesterol preparations containing a lipoteichoic acid from streptococcus

• US 6,214,978 B1
• Filed: 01/15/1999
• Issued: 04/10/2001
• Est. Priority Date: 01/30/1995
• Status: Expired due to Term

• Current Assignee: Lunamed AG
• Original Assignee: Lunamed AG
• Inventors: Rothlisberger, Peter, Truog, Peter
• Primary Examiner(s): Lee, Howard C.
• Application Number:
  US09/232,106
• Time in Patent Office: 816 Days
• Field of Search: 536/4.1, 536/17.1, 536/116, 536/117, 536/120, 514/25
• US Class Current: 536/4.1
• 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 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 38/51 Lyases (4)
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 15/04 attached to an oxygen atom of the saccharide radical
• CPC Class Codes: C07H 15/06 being a hydroxyalkyl group esterified by a fatty acid
• CPC Class Codes: C12P 19/44 Preparation of O-glycosides, e.g. glucosides polysaccharides and not substituted disaccharides C12P19/04, C12P19/12
• CPC Class Codes: Y10S 435/885 Streptococcus

Abstract

The invention concerns a new lipoteichoic acid which can be isolated from the new Streptococcus sp DSM 8747. The new LTA is called LTA-T. It has a lipid anchor, which is a galacto-furanosyl-beta-1-3-glycerol with different rests of fatty acids esterified in the two adjacent hydroxy groups in the glycerol moiety and a non-glycosylated, linear, unbranched GroP chain with an unusual short hydrophilic GroP chain. The hydrophilic backbone consists of only 10 glycerophosphate units esterified with D-alanine in an extent of 30%. The invention further concerns a pharmaceutical composition with the new LTA-T, optionally together with a monokine and/or hyaluronidase, a method of treating cancer comprising administration of an antitumor effective amount thereof, a method of producing the new compound and the new pharmaceutical composition, two degradation products of the new LTA-T and their use, and the new Streptococcus strain from which the new compound can be isolated.

Claims

1. A lipoteichoic acid (LTA) of the Formula I,

(i) wherein R₁ is hydrogen or D-alanyl with a molar ratio to phosphorus of about 0.27 to 0.35, R₂ are the residues of saturated or unsaturated fatty acids with 12, 14, 16 or 18 carbon atoms, and the mean value for n is 9;

and (ii) salts thereof.

2. The LTA according to claim 1 present in the form of a physiologically acceptable salt.

3. The LTA of claim 1 derived from (i) positively charged ions including alkali metal ions, alkaline earth metal ions, or positively charged primary, secondary, tertiary or quaternary ammonium ions or (ii) acid addition salts thereof.

4. The LTA of claim 3 in which said ions comprise sodium, potassium, calcium, zinc, or ammonium ions;

or lower alkyl ions comprising alkyls of 1 to 4 carbon atoms including methyl, ethyl, methyl-ethyl, propyl, or butyl-ammonium ions.

5. A method for making the LTA according to claim 1, comprising isolating the LTA from Streptococcus sp DSM 8747.

6. A pharmaceutical preparation comprising the LTA according to claim 1 or a physiologically acceptable salt thereof in dosage unit form.

7. A pharmaceutical preparation according to claim 6 in combination with an alpha-interferon.

8. A pharmaceutical preparation according to claim 6 in combination with hyaluronidase.

9. A pharmaceutical preparation according to claim 6 in combination with alpha-interferon and hyaluronidase.

10. A method of treating cancer comprising administering an antitumor effective amount of the LTA according to claim 1 or a physiologically acceptable salt thereof to a patient suffering from a tumor or a malignant cell thereof.

11. A method of lowering the blood cholesterol level in a human patient comprising administering a cholesterol lowering amount of LTA according to claim 1 or a physiologically acceptable salt thereof to such human patient in need thereof.

12. A deacylated dLTA-T according to claim 1 wherein R¹ and R² are hydrogen or a salt thereof.