# US 4,378,433 A · Method for producing zinc etheromycin from fermentation broths

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- Number: US 4,378,433 A
- Document ID: US4378433A
- Status: Granted
- Kind: A
- Application number: 06/139,565
- Filed: 1980-04-11
- Granted: 1983-03-29
- Earliest claimed: 1980-04-11
- Assignees: International Minerals & Chemical Corp.
- Inventors: Jerome L. Martin
- Web page: https://patentgrep.com/patent/US4378433A

## CPC

- C07H 23/00: Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00)
- A23K 20/195: Antibiotics
- Y10S 435/898: Streptomyces hygroscopicus
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- A23K: FODDER
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Zinc complexes of glycolic monovalent monoglycoside polyether antibiotics are provided for use as coccidiostats and growth-promoting agents when administered to poultry and for use as active agents for improving cardiovascular function in animals. Zinc complexes of the type disclosed can be prepared by adding soluble zinc salt to a fermentation beer containing the glycolic monovalent monoglycoside polyether antibiotic to thereby form an insoluble, recoverable biomass containing the desired zinc antibiotic complex.

## Claims

### Claim 1

A method for producing a zinc complex of etheromycin said method comprising:
(a) fermenting a fermentation broth inoculated with a Streptomyces hygroscopicus microorganism capable of producing etheromycin by fermentation of the broth for a period of time and under suitable fermentation conditions in order to produce said antibiotic in said fermentation broth; and
(b) providing in said etheromycin containing fermentation broth a water-soluble zinc salt in an amount sufficient to form a zinc complex of etheromycin, which complex is insoluble in the fermentation broth.

### Claim 2 (depends on 1)

A method in accordance with claim 1 further including the step of recovering said insoluble zinc complex from said fermentation broth.

### Claim 3 (depends on 1)

A method in accordance with claim 1 wherein the fermentation of the inoculated broth is conducted at a temperature of from about 25.degree. C. to 35.degree. C. and at a pH of from about 6.5 to 7.5.

### Claim 4 (depends on 2, 3)

A method in accordance with claim 2 or 3 wherein the zinc salt is added to the fermentation broth and is selected from zinc chloride and zinc sulfate.

### Claim 5 (depends on 4)

A method in accordance with claim 4 wherein the pH of the fermentation broth is adjusted to within the range of from about 6.5 to 7.5 after said zinc salt is provided in said fermentation broth.

### Claim 6 (depends on 2)

A method in accordance with claim 2 wherein the insoluble zinc antibiotic complex is recovered from said fermentation broth as part of a biomass which additionally contains insoluble zinc complexes of residual nitrogen-containing compounds present in the fermentation broth.

### Claim 7 (depends on 6)

A method in accordance with claim 6 wherein water soluble zinc salt is added to the fermentation broth in an amount sufficient to provide a zinc content of from about 3 to 12 percent by weight on a dry basis in the biomass recovered from said fermentation broth.

### Claim 8 (depends on 1)

A method in accordance with claim 1 further including the steps of:
(c) acidifying the fermentation broth containing the insoluble zinc complex to form the acidic form of etheromycin;
(d) extracting the etheromycin from the broth into a water-insoluble organic solvent;
(e) adding a lower aliphatic alcohol to the organic solvent containing the etheromycin, the alcohol containing a soluble zinc salt in an amount sufficient to form a zinc complex of etheromycin; and
(f) recovering the formed zinc complex of etheromycin from the organic solvent-alcohol mixture.

### Claim 9 (depends on 8)

A method in accordance with claim 8 wherein the aliphatic alcohol is methanol.

### Claim 10 (depends on 8, 9)

A method in accordance with claims 8 or 9 wherein the organic solvent is butyl acetate.

### Claim 11 (depends on 8)

A method in accordance with claim 8 wherein the fermentation broth is acidified to a pH of 4.0 or less.

### Claim 12 (depends on 8)

A method in accordance with claim 8 wherein the zinc salt used in step (e) is zinc chloride.

### Claim 13 (depends on 8)

A method in accordance with claim 8 further including the step of adding an aliphatic alcohol to the organic solvent containing the antibiotic prior to step (e).

### Claim 14 (depends on 8)

A method in accordance with claim 8 further including the steps of extracting the etheromycin from the organic solvent into an aqueous alkaline solution and then extracting the etheromycin from the aqueous alkaline solution into a second water-insoluble organic solvent.

### Claim 15 (depends on 14)

A method in accordance with claim 14 wherein the aqueous alkaline solution contains a metal hydroxide selected from the group consisting of sodium hydroxide and potassium hydroxide.

### Claim 16 (depends on 14)

A method in accordance with claim 14 wherein the second water-insoluble organic solvent is selected from the group consisting of butyl acetate and methyl tertiary butyl ether.

### Claim 17

A method for producing a zinc complex of etheromycin which comprises complexing etheromycin zinc or zinc precursor under zinc-etheromycin complexing conditions to produce a zinc complex of etheromycin, the zinc-etheromycin complexing conditions including a fermentation broth in which etheromycin is produced.

### Claim 18 (depends on 17)

The method of claim 17 wherein the zinc or zinc precursor is water-soluble zinc salt.
