Antibiotic called "chloropolysporin", a process for its preparation, and its therapeutic and veterinary use

• US 4,557,933 A
• Filed: 07/03/1984
• Issued: 12/10/1985
• Est. Priority Date: 07/15/1983
• 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, Iwado, Seigo, Katayama, Toshiaki, Enokita, Ryuzou
• Primary Examiner(s): Goldberg, Jerome D.
• Application Number:
  US06/627,439
• Time in Patent Office: 525 Days
• Field of Search: 424/118, 435/169
• US Class Current: 424/118
• CPC Class Codes: A23K 20/195 Antibiotics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C12N 1/205 Bacterial isolates
• CPC Class Codes: C12P 1/06 by using actinomycetales
• CPC Class Codes: C12P 21/005 Glycopeptides, glycoproteins
• CPC Class Codes: C12R 2001/01 Bacteria or Actinomycetales ; using bacteria or Actinomycetales

Abstract

A novel compound, called chloropolysporin, has antibiotic properties and would appear to be a member of the class of glycopeptide antibiotics containing chlorine. It may be produced by cultivating a suitable strain of microorganism of the genus Micropolyspora, especially Micropolyspora sp. SANK 60983 (FERM BP-538). It 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 and characterized by the following properties:

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

(b) specific rotation;

[α

]²⁵ -94.4°

(C═

0.09, 50%v/v aqueous methanol, sodium D-line);

(c) elemental analysis;

C, 49.88%;

H, 5.44%;

N, 5.65%;

Cl, 5.20%;

(d) on acid hydrolysis it yields;

neutral saccharides;

glucose, mannose and rhamnose;

amino acids;

monochloro-monohydroxy-phenylglycine;

(e) ultraviolet absorption spectrum;

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

_max at 280 nm (E_1cm =45) in a 0.01N solution of hydrochloric acid and at 300 nm (E_1cm =54.2) in a 0.01N aqueous solution of sodium hydroxide, the absorbences, E, being measured at a concentration of 1% w/v;

(f) infrared absorption spectrum;

the infrared absorption spectrum (ν

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 400 MHz in a mixture of deuterium oxide and deuterohydrochloric acid of pH value about 3.0, using sodium 2,2-dimethyl-2-silapentane-5-sulfonate 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 0.1M 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.

2. A process for producing the antibiotic substance chloropolysporin as defined in claim 1, which comprises cultivating under aerobic conditions Micropolyspora sp. SANK 60983 (FERM BP-538, FERM P-6985) in a culture broth therefor at a temperature of from 24°

to 30°

C. at which said microorganism is viable to produce a sufficient amount of chloropolysporin in said culture broth and collecting said chloropolysporin from said culture broth.

3. A process as claimed in claim 2, wherein said temperature is about 28°

C.

4. A pharmaceutical composition comprising a pharmaceutically effective amount of the antibiotic substance chloropolysporin as defined in claim 1 in admixture with a pharmaceutical carrier or diluent.

5. A method for the treatment or prophylaxis of bacterial infections by administering an antibiotically effective amount of the antibiotic substance chloropolysporin as defined in claim 1 to an animal.

6. A method of promoting the growth of a farm animal by the oral administration thereto of an antibiotically effective amount of the antibiotic substance chloropolysporin as defined in claim 1.

7. A veterinary composition comprising a veterinary effective amount of the antibiotic substance chloropolysporin as defined in claim 1 in admixture with a veterinary carrier or diluent.