420 VITAMIN Bi2 



3. Addition of Cobalt to the Fermentation 



Vitamin B12 contains about 4 % cobalt. The natural cobalt content of the 

 normal ingredients of the broth is very small. The addition of small amounts 

 of cobalt salts to the broth increases the Br> production; the increase goes 

 up to seventeen times the amount without addition of cobalt. The optimal 

 concentration is about 2 parts of cobalt per million of the nutrient medium ; 

 4 p.p.m. already decreases the simultaneous production of streptomycin 

 to nearly one-fourth. ^^' "• ^^ 



4. B12 FROM Activated Sludge 



Porges^^ and his group were the first to show that activated sludge from 

 sewage disposal plants contains considerable amounts of Bio. No industrial 

 firm, however, has tried to use this source. In June, 1953, the Sewerage 

 Commission of Milwaukee, Wisconsin, announced-^ the erection of a pilot 

 plant to this end, and shortly afterward a United States patent on the 

 process was granted to Miner and Wolnak.^i It seems likely that the process 

 will have industrial success only when the enormous amounts of solid raw 

 material are disposed of as a paying product (used as fertilizer, Milor- 

 ganite). 



B. PATENT SITUATION 



About twenty United States patents protect methods of production and 

 isolation of B12, whereas the compound itself is protected in this country 

 by a product claim (Rickes and Wood^), defining B12 clearly by its absorp- 

 tion spectrum and biological activity. Merck & Co., Inc., leads the field 

 by owning the product claim and the addition of cobalt to the fermentation 

 nutrient. 1'' 



C. PRODUCTION AND PRICES 



In the short time of five years vitamin B12 has become one of the most 

 important vitamins, therapeutically as well as economically. In 19ol in this 

 country alone 48 lb. with a sales value of 11 million dollars were sold; the 

 production in 1952 was 94 lb., and the sales totaled 61 lb. with an estimated 

 value of 13 to 14 million dollars. 



" T. R. Wood and D. Hendlin, (to Merck & Co., Inc.),U. S. Pat. 2,595,499 (May 6, 



1952). 

 18 The Distillers Company Ltd., Edinburgh, Swiss Pat. 287,713 (April 16, 1953). 

 i» S. R. Hoover, L. B. Jasewicz, and N. Porges, Science 114, 213 (1951). 

 ^^ Chem. Eng. News 31, 2689 (1953); Drug Trade Neivs, manufact. section, p. 69 



(July 6, 1953). 

 " C. S. Miner and B. Wolnak, (to Sewerage Commission of Milwaukee), U. S. P.it. 



2,646,386 (July 21, 1953). 



