Antibiotics called "chloropolysporins B and C", a process for their preparation, and their therapeutic and veterinary use

• US 5,013,550 A
• Filed: 02/06/1990
• Issued: 05/07/1991
• Est. Priority Date: 01/11/1985
• Status: Expired due to Fees

• Current Assignee: Sankyo Company Limited (Daiichi Sankyo Company Limited)
• Original Assignee: Sankyo Company Limited (Daiichi Sankyo Company Limited)
• Inventors: Okazaki, Takao, Nakajima, Mutsuo, Torikata, Akio, Haneishi, Tatsuo
• Primary Examiner(s): Doll, John
• Assistant Examiner(s): Chan, Christina
• Application Number:
  US07/475,688
• Time in Patent Office: 455 Days
• Field of Search: 530/317, 530/322, 514/8, 514/9, 424/117, 424/118
• US Class Current: 424/117
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 9/008 directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin
• CPC Class Codes: C12N 1/205 Bacterial isolates
• CPC Class Codes: C12R 2001/01 Bacteria or Actinomycetales ; using bacteria or Actinomycetales

Abstract

Novel compounds, called chloropolysporins B and C, and salts thereof have antibiotic properties and would appear to be members of the class of glycopeptide antibiotics containing chlorine. They may be produced by cultivating a suitable strain of microorganism of the genus Micropolyspora, especially Micropolyspora sp. SANK 60983 (FERM BP-538). They may be combined with conventional pharmaceutically acceptable carriers or diluents for therapeutic use or incorporated into edible excipients, such as feed or water, for use as a growth-promoting agent, especially for farm animals.

Claims

1. An antibiotic substance named chloropolysporin B and pharmaceutically acceptable salts thereof, which, as its sulfate, is characterized by the properties:

(a) it takes the form of an amphoteric white powder, soluble in water;

(b) specific rotation;

[α

]²⁵ -64.5°

(C=1.04, 0.1 N aqueous hydrochloric acid, sodium D-line);

(c) elemental analysis;

C, 48.33%;

H, 5.05%;

N, 5.48%;

Cl, 5.11%;

S, 1.00%;

(d) on acid hydrolysis it yields;

neutral saccharides;

glucose, mannose and rhamnose;

amino acids;

3-chloro-4-hydroxyphenylglycine and N-methyl-p-hydroxyphenylglycine;

(e) ultraviolet absorption spectrum;

as illustrated in FIG. 1 of the accompanying drawings, having an absorption maximum λ

_max at 280 nm (E_1cm =51) in a 0.1 N solution of hydrochloric acid, the absorbence, E, being measured at a concentration of 1% w/v;

(f) infrared absorption spectrum;

the infrared absorption spectrum (υ

cm^-1) measured on a KBr disc is as shown in FIG. 2 of the accompanying drawings;

(g) nuclear magnetic resonance spectrum;

the nuclear magnetic resonance spectrum (δ

ppm), measured at 270 MHz in deuterated dimethyl sulfoxide using tetramethylsilane as the internal standard, is as illustrated in FIG. 3 of the accompanying drawings;

(h) solubility;

soluble in water and methanol, sparingly soluble in acetone, and insoluble in ethyl acetate, chloroform and benzene;

(i) color reactions;

positive in Ninhydrin and Rydon-Smith reactions;

(j) thin layer chromatography;

Rf value=0.65, using a cellulose sheet (Eastman) as adsorbent and a 15;

10;

3;

12 by volume mixture of butanol, pyridine, acetic acid and water as the developing solvent;

(k) high voltage paper electrophoresis;

using Toyo'"'"'s filter paper No. 51A in a 0.1 M tris-hydrochloric acid buffer solution of pH 7.5 (3300 volt/60 cm, 1 hour);

the migration distance (detected by bioautography with Bacillus subtilis PCI

     219) from the origin to the cathode was 4 cm;

(l) molecular formula;

C₈₃ H₈₉ O₃₄ N₈ Cl₃. 0.5H₂ SO₄. 10H₂ O;

(m) molecular weight;

the molecular weight, measured by FAB-MS, was 1846 (MH⁺,

     1847).

2. A pharmaceutical or veterinary composition comprising the antibiotic substance chloropolysporin B or a salt thereof in an antibiotic effective amount as defined in claim 1 in admixture with a pharmaceutical or veterinary carrier or diluent.

3. A method for the treatment or prophylaxis of bacterial infections by administering an antibiotic effective amount of the antibiotic substance chloropolysporin B or a salt thereof as defined in claim 1 to an animal.

4. A method of promoting the growth of a farm animal by the oral administration of an effective amount of the antibiotic substance chloropolysporin B or a salt thereof as defined in claim 1 to said animal.

5. An antibiotic composition comprising 0.1 to 1.0 grams of the chloropolysporin B or salt thereof of claim 1 in a pharmaceutical carrier or diluent.

6. A compound of the formula:

##STR2## wherein;

R¹ represents a ristosamine residue;

R² represents a mannose residue;

R³ represents a glucose residue; and

R⁴ represents a rhamnose residue;

or a pharmaceutically acceptable salt thereof.