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

• US 4,918,054 A
• Filed: 07/11/1989
• Issued: 04/17/1990
• 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: Nakajima, Mutsuo, Torikata, Akio, Enokita, Ryuzo, Katayama, Toshiaki, Okazaki, Takao, Haneishi, Tatsuo, Iwado, Seigo
• Primary Examiner(s): Lee, Lester L.
• Assistant Examiner(s): Chan, Christina
• Application Number:
  US07/379,656
• Time in Patent Office: 280 Days
• Field of Search: 514/8, 514/9, 530/317, 530/321, 530/322, 424/117, 424/118
• US Class Current: 514/2.4
• 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 miroorganism 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 C and pharmaceutically acceptable salts thereof, which, as its sulfate, is characterized by the following properties:

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

(b) specific rotation;

[α

]²⁵ -64.4°

(C=1.08, 0.1N aqueous hydrochloric acid, sodium D-line);

(c) elemental analysis;

C, 50.53%;

H, 4.69%;

N, 6.14%;

Cl, 5.62%;

S, 1.12%;

(d) on acid hydrolysis it yields;

neutral saccharides;

glucose and mannose;

amino acids;

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

(e) ultraviolet absorption spectrum;

as illustrated in FIG. 4 of the accompanying drawings, having an absorption maximum λ

_max at 280 nm (E_1cm =57) in a 0.1N solution of hydrochloric acid, the absorbence, 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. 5 of the accompanying drawings;

(g) nuclear magnetic resonance spectrum;

the nuclear magnetic resonance spectrum (δ

ppm), measured at 400 MHz in deuterated dimethyl sulfoxide using tetramethylsilane as the internal standard, is as illustrated in FIG. 6 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) molecular formula;

C₇₇ H₇₉ O₃₀ N₈ Cl₃.0.5H₂ SO₄.5H₂ O;

(l) molecular weight;

the molecular weight, measured by FAB-MS, was 1700 (MH⁺,

     1701).

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

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

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

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

2. 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 hydrogen atom;

or a pharmaceutically acceptable salt thereof.