This invention relates to a cobalt mixture that is a new source of cobalt for domesticated ruminant animals. Taking advantage of a mixture of cobalt salts that are a combination of fast cobalt release and slow cobalt release in the rumen of ruminant animals the cobalt is available to the rumen bacteria of a ruminant animal over a steady period of time for the bacteria to produce Vitamin B12 needed for the animal health and milk production during lactation.
Vitamin B12 is unique among the vitamins in that it contains not only an organic molecule, but also the essential trace element cobalt. Vitamin B12 is not made by either plants or animals and can be synthesized by only a few species of microorganisms. Bacteria in the human intestinal tract can make enough Vitamin B12 for normal daily requirements from inorganic cobalt salts in the diet. Vitamin B12 is also made in large amounts by rich populations of bacteria in the rumen of ruminant animals and in the cecum of other herbivorous species.
Vitamin B12 participates in many biochemical processes that are essential for life. It acts as a co-enzyme for several enzymes which catalyze the shift of a hydrogen atom from one carbon atom to an adjacent one in exchange for an alkyl, carboxyl, hydroxyl or amino groups. Deficiency of Vitamin B12 results in the development of the serious disease pernicious anemia. Pernicious anemia, as the name implies, involves a low concentration of hemoglobin resulting from the condition, but the effects also include serious disturbances of the central nervous system that may result in abnormal sensations, motion, and in humans, thought.
Vitamin B12 is known to have a positive effect on lactation performance of dairy cows, see for example the Journal of Dairy Science, 2005 February; 88(2): 671-6, Girard et al. which shows that in early lactation the supply of Vitamin B12, if deficient, limits the lactation performance of cows. Since cobalt is needed in animal nutrition as a key component to Vitamin B12 production it therefore follows that ruminants need adequate dietary supply of cobalt for effective animal nutrition and efficient lactation performance. In ruminants, the soluble portion of the ruminal material (solids and liquids) is turned over faster than the solids. This means that highly soluble sources of cobalt will remain in the rumen less time than insoluble forms. This invention relates to the ability of a ruminant's bacteria to produce Vitamin B12. The need for increased B12 production can be seen by the increased performance when B12 is injected, see Journal Dairy Science article previously cited.
A method and composition which is a unique source of cobalt for enhanced production of Vitamin B12 in the rumen. It has the advantage of a slow release source of cobalt combined with a fast release source of cobalt. The fast cobalt ion release source which is a soluble source of cobalt is turned over faster in the rumen than the solids cobalt sources are turned over. Thus slower release, for example longer polymer strands of cobalt ligands, are digested over a longer period of time, giving slower release of the cobalt. In this way, a portion of the cobalt mixture is soluble and another portion substantially insoluble; the insoluble portion will remain in the rumen longer. As the bacteria consume, for example, a polysaccharide of cobalt, it will release the cobalt for B12 production. Alternatively, non-rumen degradable polymers like polyacrylic acid would just slowly release cobalt. Surprisingly such control or slow release of cobalt to the rumen bacteria in combination with a faster release such as a soluble salt of cobalt source like a monomeric sugar, is shown by data to have greater B12 production than an all soluble cobalt source, or an all insoluble source.
This invention involves a mixture of a quick release cobalt source and a slow release cobalt source, which when fed to a ruminant animal, allows some cobalt ions (the quick release) to immediately be used by the rumen bacteria in making Vitamin B12, with the balance to slowly release additional cobalt ions as it is more slowly metabolized by the microorganisms of the rumen. Studies have surprisingly demonstrated this combination of quick release and slow release cobalt sources results in more efficient and effective production of Vitamin B12 than either source alone. Not wishing to be bound by any theory, it is believed this occurs because the quick release passes through the rumen faster than the bacteria can metabolize it to Vitamin B12 thus much of it “wasted”. In contrast the slow release source of cobalt occurs as the rumen microorganisms gradually metabolize larger molecules of the more insoluble polymers releasing the cobalt to make Vitamin B12. In the case of all slow release time is “wasted” with limited cobalt available to result in less B12.
Quick release sources of cobalt include soluble inorganic and organic sources of cobalt such as cobalt chloride, cobalt sulfate, cobalt acetate and other fast release (soluble) cobalt monomer sugar complexes like for example cobalt glucoheptonate or cobalt gluconate, as shown in the assignees earlier U.S. Pat. No. 4,678,854, of Jul. 7, 1987, the disclosure of which is incorporated herein by reference.
Slow release cobalt sources include insoluble and partially soluble cobalt polymer ligands such as those of alginic acid, pectin, polyacrylic and carboxymethycellulose complexes with cobalt, as well as other cobalt inclusive polymer complexes with pendant carboxylic acid groups, all of which are largely insoluble.
The quick release cobalt source allows the cobalt to immediately be available to the bacteria from the liquid in the rumen, although much of it passes through so quickly that it cannot all be used. The slow release cobalt source remains in the rumen and passes through only when the microorganisms metabolize the polymer or the salt slowly releases the cobalt which results in a gradually available cobalt source for the making of Vitamin B12 or a gradual release of cobalt from the insoluble form.
The key is to have some polymer bound soluble cobalt and some portion of that being insoluble. This creates a situation where the soluble fraction can immediately start being utilized by the bacteria. As the fluid is turned over in the rumen the cobalt available to the bacteria in an all soluble (inorganic or low molecular weight ligands) will be removed from the rumen. By this time the bacteria will have been degrading the polymer from the polymer bound cobalt releasing this cobalt fraction to the rumen fluid. In essence this “insoluble” fraction is a controlled release source of cobalt. Surprisingly it is best to have both types of cobalt present to optimize vitamin B12 production. The polymer bound insoluble portion can be derived from any acid containing polymer. The prime examples are pectin and alginic acid.
The examples set forth below are offered as illustrative of embodiments of the invention with the understanding that they are not limiting as other examples could as well be set forth. It is believed, however, they are representative of the invention and data produced by use of the invention.
Cobalt Pectin—2 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (59.92 g, 1.49 mols). To this alkaline solution pectin (30.01 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (80.42 g, 0.338 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
This milk production increase was statistically significant.
Cobalt Pectin—1 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (60.02 g, 1.50 mols). To this alkaline solution pectin (30.05 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (40.44 g, 0.170 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Pectin—0.66 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (60.09 g, 1.50 mols). To this alkaline solution pectin (30.03 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (26.50 g, 0.112 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Pectin—0.5 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (59.96 g, 1.49 mols). To this alkaline solution pectin (29.99 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (20.11 g, 0.085 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Alginic—2 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (60.01 g, 1.50 mols). To this alkaline solution alginic acid (29.90 g, 0.168 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark yellow brown suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (80.41 g, 0.338 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Alginic—1 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (59.95 g, 1.49 mols). To this alkaline solution alginic acid (30.01 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark yellow brown suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (40.15 g, 0.168 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Alginic—0.66 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (59.99 g, 1.50 mols). To this alkaline solution alginic acid (29.98 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark yellow brown suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (26.53 g, 0.112 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Alginic—0.5 eq. Cobalt, 10 eq. NaOH, 12 hours at 20° C.
To 750 mL of dI water is added sodium hydroxide (60.02 g, 1.50 mols). To this alkaline solution alginic acid (30.06 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark yellow brown suspension which is allowed to stir for 12 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl acid at this point solid CoCl2 6H2O (20.08 g, 0.085 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Polyacrylic Acid—2 eq. Cobalt, 1 eq. NaOH
To 750 mL of dI water is added sodium hydroxide (2.04 g, 0.051 mols). To this alkaline solution 50% polyacrylic acid (7.57 g, 0.051 mols of carboxylic acid subunits) is added in one portion. The clear solution is allowed to stir for 10 minutes at which point CoCl2 6H2O (24.28 g, 0.102 mols) is added in one portion. The pink suspension is stirred for an additional one hour at room temperature and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Polyacrylic Acid—1 eq. Cobalt, 1 eq. NaOH
To 750 mL of dI water is added sodium hydroxide (2.10 g, 0.051 mols). To this alkaline solution 50% polyacrylic acid (7.54 g, 0.051 mols of carboxylic acid subunits) is added in one portion. The clear solution is allowed to stir for 10 minutes at which point CoCl2 6H2O (12.14 g, 0.051 mols) is added in one portion. The pink suspension is stirred for an additional one hour at room temperature and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Polyacrylic Acid—0.66 eq. Cobalt, 1 eq. NaOH
To 750 mL of dI water is added sodium hydroxide (2.04 g, 0.051 mols). To this alkaline solution 50% polyacrylic acid (7.60 g, 0.051 mols of carboxylic acid subunits) is added in one portion. The clear solution is allowed to stir for 10 minutes at which point CoCl2 6H2O (8.00 g, 0.034 mols) is added in one portion. The pink suspension is stirred for an additional one hour at room temperature and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Polyacrylic Acid—0.5 eq. Cobalt, 1 eq. NaOH
To 750 mL of dI water is added sodium hydroxide (2.01 g, 0.051 mols). To this alkaline solution 50% polyacrylic acid (7.57 g, 0.051 mols of carboxylic acid subunits) is added in one portion. The clear solution is allowed to stir for 10 minutes at which point CoCl2 6H2O (6.08 g, 0.102 mols) is added in one portion. The pink suspension is stirred for an additional one hour at room temperature and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Pectin 1 eq. Cobalt (50% Organic/50% Inorganic)—2.5 hours at 70° C.—1 eq. Base—No HCl
To 370 mL of dI water is added sodium hydroxide (6.74 g, 0.168 mols). To this alkaline solution pectin (30.01 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2.5 hours at 70° C. At this point solid CoCl2 6H2O (40.21 g, 0.169 mols) is added to the reaction in one portion and the pH of 12.31 is consequently reduced to 5.868. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels and molecular weight.
Cobalt Pectin—1 eq. Cobalt, 1 eq. NaOH, 2 hours at 70° C., HCl Quench
To 370 mL of dI water is added sodium hydroxide (6.79 g, 0.169 mols). To this alkaline solution pectin (40.49 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2 hours at 70° C. The pH is adjusted to 8.8 with 12M HCl (10.5 mL, 126 mmols) acid at this point solid CoCl2 6H2O (40.08 g, 0.170 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Pectin—0.66 eq. Cobalt, 1 eq. NaOH, 2 hours at 70° C., No HCl Quench
To 370 mL of dI water is added sodium hydroxide (6.70 g, 0.168 mols). To this alkaline solution pectin (40.45 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2 hours at 70° C. At this point solid CoCl2 6H2O (26.40 g, 0.112 mols) is added to the reaction in one portion and the pH of 12.45 is consequently reduced to 5.938. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels and molecular weight.
Cobalt Pectin—0.5 eq. Cobalt, 1 eq. NaOH, 2 hours at 70° C., No HCl Quench
To 370 mL of dI water is added sodium hydroxide (6.81 g, 0.169 mols). To this alkaline solution pectin (40.53 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2 hours at 70° C. At this point solid CoCl2 6H2O (20.07 g, 0.085 mols) is added to the reaction in one portion and the pH of 12.40 is consequently reduced to 5.871. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels and molecular weight.
Cobalt Pectin—1 eq. Cobalt, 2 eq. NaOH, 2 hours at 70° C., HCl Quench
To 370 mL of dI water is added sodium hydroxide (13.51 g, 0.338 mols). To this alkaline solution pectin (40.46 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2 hours at 70° C. The pH is adjusted to 8.8 with 12M HCl (21.5 mL, 258 mmols) acid at this point solid CoCl2 6H2O (39.91 g, 0.169 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Pectin—1 eq. Cobalt, 4 eq. NaOH, 2 hours at 70° C., HCl Quench
To 370 mL of dI water is added sodium hydroxide (27.01 g, 0.68 mols). To this alkaline solution pectin (40.54 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2 hours at 70° C. The pH is adjusted to 8.8 with 12M HCl (43 mL, 516 mmols) acid at this point solid CoCl2 6H2O (39.91 g, 0.169 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Pectin—1.5 eq. Cobalt, 1 eq. NaOH, 2 hours at 70° C., HCl Quench
To 370 mL of dI water is added sodium hydroxide (6.74 g, 0.168 mols). To this alkaline solution pectin (40.48 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2 hours at 70° C. The pH is adjusted to 8.8 with 12M HCl (10.8 mL, 130 mmols) acid at this point solid CoCl2 6H2O (60.03 g, 0.26 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
Cobalt Pectin—1 eq. Cobalt, 1 eq. NaOH, 2 hours at 20° C., HCl Quench
To 370 mL of dI water is added sodium hydroxide (6.81 g, 0.169 mols). To this alkaline solution pectin (40.5 g, 0.169 mols of carboxylic acid subunits) is added slowly so as to disperse finely upon the surface of the solution. The fine dispersion quickly becomes a dark orange suspension which is allowed to stir for 2 hours at 20° C. The pH is adjusted to 8.8 with 12M HCl (10.5 mL, 126 mmols) acid at this point solid CoCl2 6H2O (40.08 g, 0.170 mols) is added to the reaction in one portion. The resulting pink suspension is stirred for an additional 1 hour and then dried at 88° C. for 12 hours. The final blue powder is homogenized and analyzed for cobalt levels.
The pre and post treatment data after receiving the given cobalt source by sheep is shown in
As earlier explained Examples 1-24 are illustrative only. They are offered to provide support for the attached claims. Applicant intends to rely upon the doctrine of equivalents for proper scope. It is understood that other cobalt sources which provide quick release and slow release in combination when fed to ruminants are contemplated as long as they allow performance of the invention to enhance Vitamin B12 production in ruminants especially during lactation.
Number | Name | Date | Kind |
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4678854 | Abdel-Monem | Jul 1987 | A |
20130339216 | Lambert | Dec 2013 | A1 |
Number | Date | Country |
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866924 | May 1961 | GB |
9111915 | Aug 1991 | WO |
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Number | Date | Country | |
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20190014797 A1 | Jan 2019 | US |