Food or edible material: processes – compositions – and products – Treatment of live animal
Reexamination Certificate
1999-08-03
2001-04-17
Sayala, Chhaya D. (Department: 1761)
Food or edible material: processes, compositions, and products
Treatment of live animal
C426S636000, C426S807000
Reexamination Certificate
active
06217915
ABSTRACT:
FIELD OF THE INVENTION
The invention is directed toward feed and feed additives for ruminant and monogastric animals, including humans, which increase the amount of butyric acid and non-digestible oligosaccharides in the intestine.
DESCRIPTION OF THE PRIOR ART
n-Butyric acid (n-butanoic acid) is known as a source of energy for the intestinal mucosa of animals. In general, increasing the concentration of butyric acid within the lumen of the intestine results in increased mucosal growth and an increase in the aspect ratio of the mucosal villi and the depth of the cripts. This, in turn, increases the surface area of the mucosa and hence the ability of the mucosa to absorb nutrients from within the contents of the intestine.
Tributyrin, also known as glyceryl tributyrate or tributyl glycerol, has the following formula:
Tributyrin can be prepared synthetically by the esterfication of glycerol in the presence of excess butyric acid. Tributyrin is readily available in bulk quantities from several national and international suppliers, such as Aldrich, Milwaukee, Wis. Acid and/or enzymatic hydrolysis of tributyrin yields three molar equivalents of butyric acid.
Lactitol, the common name for the oligosaccharide 4-&bgr;-D-galactosyl-D-sorbitol, has the following formula:
Lactitol is prepared synthetically by the hydration of lactose. Lactitol is readily available in bulk quantities from numerous national and international suppliers, such as Purac, Arlington Heights, Ill. In one application it is used as a non-caloric sweetener in foods such as ice cream. Host 62-galactosidases found in the small intestines of mammals degrade lactitol to only an extremely limited extent. As a consequence, lactitol is not absorbed to any appreciable extent by the mammalian gut. However, lactitol is utilized as an energy source by the microflora residing within the intestinal lumen of mammals. Other oligosaccharides containing a galactosyl unit which is &bgr;-linked to another sugar moiety (such as lactulose) behave similarly.
Several prior art references describe the addition of lactitol to animal feeds. For instance, EPA 0 218 324 A1 describes a growth-stimulating animal feed containing lactitol. This reference specifically states, at page 3, lines 12-14, that “the addition of lactitol to the feed of a monogastric domestic animal improves the growth of the animal.” See also EPA 0 464 362 A1 for a similar discussion by the same inventors.
Piva et al. (1996) “Lactitol Enhances Short-Chain Fatty Acid and Gas Production by Swine Cecal Microflora to a Greater Extent When Fermenting Low Rather Than High Fiber Diets,” J. Nutr. 126:280-289, report the addition of lactitol to swine feed in an effort to enhance cecal fermentation. The results presented in this paper indicate that lactitol is more beneficial as a feed additive when used in combination with a low-fiber diet as compared to a high-fiber diet.
European Patent Application 0 661 004 A1 describes an animal feed composition containing lactitol and amino acids. The specification states that any sugar alcohol, including lactitol, can be used in the composition, so long as the sugar alcohol does not undergo aminocarbonylation with the amino group of amino acids. The composition is puported to improve the “nutritional condition” of an animal.
See also W. C. Sauer (1997) “The Mode and Action of Oligosaccharides in the Digestive Tract of Early-Weaned Pigs,” Alberta Agricultural Research Institute, Project No. 93-0305. This reference describes a line of research investigating the mode of action of oligosaccharides in the digestion of early-weaned pigs. The pigs' diet was supplemented with various oligosaccharides, including lactitol. This reference states that “supplementation with . . . lactitol had little effect on the apparent ileal digestibilities of amino acids and monosaccharides.” Sauer, therefore, concludes that “the supplementation of diets for weanling pigs . . . with oligosaccharides or lactitol at these levels does not affect nutrient digestibilities and bacterial populations in the small intestine.”
Of particular note regarding these prior art references is that the beneficial nature of lactitol as a feed additive for monogastric or ruminant animals, and swine in particular, has not been unambiguously established, nor has its activity been established in combination with butyrate or derivatives thereof, including tributyrin.
DEFINITIONS
The following terms are expressly defined herein:
Non-digestible oligosaccharide (NDO): A subset of pre-biotic compounds which are non-digestible by a host animal and which are comprised of two or more sugar moieties. Expressly, but not exclusively, included within the term NDO are galacto-oligosaccharides of all types, including lactitol, lactulose, lactosucrose, fructo-oligosaccharides, palatinose-oligosaccharides, glycosyl sucrose, malto-oligosaccharides, isomalto-oligosaccharides, cyclodextrins, gentio-oligosaccharides, soy-oligosaccharides, and xylo-oligosaccharides.
Pre-biotic: A non-digestible food ingredient that beneficially affects a host animal by preferentially stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves health, growth, vigor, etc. of the host animal. Pre-biotics are neither wholly hydrolyzed nor completely absorbed in the upper part of the gastro-intestinal tract.
SUMMARY OF THE INVENTION
The invention is directed to a synergistic animal feed composition comprising, in combination, tributyrin and a pre-biotic compound, preferably a non-digestible oligosaccharide (NDO). The pre-biotic compound is essentially non-digestible by the host animal but is fermentable by intestinal microflora present in the colon of the host animal. In the most preferred embodiment, the NDO is lactitol. Other preferred pre-biotic compounds include fructo-oligosaccharides and galacto-oligosaccharides other than lactitol and/or other pre-biotics.
The combination of tributyrin and a pre-biotic such as lactitol is synergistic in that the two ingredients are believed to generate butyric acid in the intestine of an animal host, while simultaneously encouraging the growth of beneficial bacteria in the lower intestine, thereby synergistically increasing the rate of weight gain and/or feed utilization of the animals. While not being bound to any particular mechanism, it is believed that tributyrin is degraded, presumably by acid hydrolysis and/or lipase activity, in the stomach and upper small intestine to yield butyric acid. The released butyric acid is then utilized as an energy source by the mucosal cells lining the intestine, resulting in improved mucosal trophism.
Pre-biotic compounds, such as NDO's, pass through the stomach and small intestine essentially unchanged and ultimately enter the large intestine, where such compounds are preferentially fermented by select microflora which inhabit the gut of animals.
The pre-biotic compounds are preferentially utilized by the lactic acid group of bacteria, including lactobacilli and bifidobacteria, which are capable of flourishing in the animal gut under the proper conditions. These beneficial bacteria produce mainly lactic acid as a fermentation end product which lowers the pH of the lower gut. This lower pH is inhospitable to many undesirable microorganims (including human and animal pathogens) which cannot survive in the lowered pH conditions. Consequently, the invention encourages a more favorable microbial balance in the GI tract. The benefical bacteria thrive due to the presence of a ready energy source such as a NDO, produce lactic acid which lowers the pH of the gut (which is also antimicrobial), and thereby competitively exclude colonization by other, potentially detrimental organisms.
These beneficial bacteria may also produce antimicrobial compounds, including bacteriocins, hydrogen peroxide, etc., which also inhibit the growth of undesirable and/or pathogenic organisms.
Another advantage of the invention is that by encouraging the vigorous growth of beneficial bacteria, this may prevent conversion of pr
Luchansky John B.
Piva Andrea
DeWitt Ross & Stevens S.C.
Leone, Esq. Joseph T.
Sayala Chhaya D.
Wisconsin Alumni Research Foundation
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