1. Field of the Invention
This invention is directed to methods and compositions for colon-targeted delivery of components.
2. Description of the Prior Art
Fructan is a non-structural carbohydrate and is a polymer of fructose. Fructans have a general structure of a glucose linked to multiple fructose units. There are several types of fructans present in nature, and they can broadly be divided into 3 groups: inulins, fructo-oligosaccharides (FOS), and neosugars.
Inulin is a polydisperse fructan extracted from plants, including chicory root, asparagus shoot, banana, dandelion, garlic, globe artichoke, Jerusalem artichoke, leek, onion, rye, salsify, and wheat, that has not been digested enzymatically by inulinase. The chemical structure of inulin is shown in FIG. 1. GFn is a glucose ending fructan chain, and n represents chain length. Inulin has a degree of polymerization (DP) in the approximate range of 2 to 60 units of β (2-1) fructose with a glucosyl terminus. The average DP is greater than 10 units.
Fructo-oligosaccharide (FOS) is partially hydrolyzed inulin with a DP in the approximate range of 2 to 20 units of β (2-1) fructose with either a glucosyl or a fructosyl terminus. The average DP is less than 10 units. Chemical structures of glucose ending fructan chains (GFn) and fructose ending chains (Fn) are shown in FIGS. 2A and 2B. Inulin is hydrolyzed with inulinase, for example, to produce fructo-oligosaccharides.
Neosugars are fructo-oligosaccharides that can be prepared, for example, by an enzymatic reaction using sucrose and the enzyme fructosyltransferase from an organism such as Aspergillus niger. The chemical structure of neosugar is shown in FIG. 3.
Neosugars have DP in the approximate range of 2 to 4 units of β (2-1) fructose with a glucosyl terminus. The average DP is about 2 to 3 units. Collectively, inulin, FOS, and neosguars are referred to herein as fructans.
Fructans are currently used as an animal feed supplement, mixed with the animal feed. Fructans are found in the feed of monogastric animals, including poultry, turkey, swine, dog, cat, horse, and bovine calf diets. (Bovine calves begin their development as monogastric mammals). Fructans are also added to food and drink for human consumption. As an oral supplement, fructans have been shown to improve weight gain, reduce fecal odor, reduce colon cancer, lower blood triglycerides, increase mineral uptake, and promote a healthy gastrointestinal system.
Fructans are essentially “non-digestible” by monogastrics; they are not digested in the stomach or small intestines. Consequently, the fructan-coated components of the instant invention are not digested in the stomach of monogastric mammals and pass directly to the colon where the fructan is fermented by organisms residing in the colon. As fructan-fermenting bacteria grow, there is a concomitant decrease in the concentrations of putrefactive bacteria such as Escherichia coli, Clostridium perfringens and Salmonella, which are widely known to produce malodorous aromatic metabolites. Bacteria that utilize fructans as a source of energy include beneficial bacteria in the genus of Bifidobacterium and Lactobacillus. Non-digestible ingredients, such as fructans, that beneficially affect the host by selectively stimulating the growth and/or activity of bacteria in the colon that can improve host health and known as “prebiotics”.
Wang et al. (Journal of Applied Bacteriology, 75:373-380, 1993) looked at mixed populations of colonic bacteria in a batch culture grown on inulin, fructo-oligosaccharide, polydextrose and starch. The type of carbohydrate used in each batch culture had no effect on total aerobic, anaerobic or Bacteriodes counts. Bifidobacteria counts were 5 to 13 times higher with batch cultures grown on fructo-oligosaccharide and inulin then polydextrose and starch. The coliform counts were 8 to 630 times lower with batch cultures grown on inulin and fructo-oligosaccharide than polydextrose and starch. Lactobacillus counts were 316-1,000 times lower in batch cultures when inulin was used as a substrate than fructo-oligosaccharide, starch and polydextrose.
In order for inulin and fructo-oligosaccharides to affect the microbial population in the colon, they must first pass through the stomach and small intestine. Samples taken from the ileum of humans receiving diets containing inulin or fructo-oligosaccharides have been shown to exhibit an 89% and 88% recovery respectfully (Ellegård et al., European Journal of Clinical Nutrition, 51:1-5, 1997). Similarly, humans receiving Neosugar in their diet have been shown to exhibit an 89% recovery in ileal samples taken (Molis et al., American Journal of Clinical Nutrition, 64:324-328, 1996). The fraction of fructan that is not recovered is digested in the gastrointestinal tract and then absorbed as glucose or fructose. The digestion may have occurred in the ileum via bacterial fermentation or by acid digestion in the stomach (Simon et al., Gastroenterology, 86:174-193, 1984). In vitro studies have shown that fructans and inulin are hydrolyzed at a low rate and a very low pH (Nilsson et al., Journal of Nutrition, 86:1482-1486, 1988).
Once the fructans reach the colon, they are fermented completely by the microbial flora. (Jenkins et al., Journal of Nutrition, 129:1431S-1433S, 1999). With fermentation of the fructans in the colon, changes occur to the microbial flora. Most notably, the Bifidobacteria sp., has been shown to increase 5 to 63 fold (Djouzi et al., British Journal of Nutrition, 78:313-324, 1997). A review by Loo et al. (British Journal of Nutrition, 81:121-132, 1999) of ten trials studying the increase in Bifidobacteria sp. in the colon of humans receiving inulin or fructo-oligosaccharide in their diets showed a statistically significant increase in Bifidobacteria sp. The average for the nine trials was an 11.8-fold increase in Bifidobacteria sp. with a high of a 22-fold increase. Other changes that were observed in colonic populations of humans receiving inulin and fructo-oligosaccharide include the significant decrease in Bacteriodes sp. and/or Clostridia sp. (Gibson et al., Journal of Nutrition, 125:1401-1412, 1995; Kleessen et al., American Journal of Clinical Nutrition, 65:1397-1402, 1997).
The increase of Bifidobacteria has been shown to be correlated to a dose response to fructan addition to the diet. Studies have shown that humans subjects exhibit no increase in Bifidobacteria sp. until their diet contains 10 grams of Neosugar per day (Bouhnik et al., Journal of Nutrition, 129:113-116, 1999). A review by Roberfroid et al. (Journal of Nutrition, 128:11-19,1998) combined data for inulin, fructo-oligosaccharide and Neosugar and concluded that log increases in counts do not correlate to daily doses administered. One variable considered to correlate with increases was the initial number of Bifidobacteria in the feces. It appeared that the lower the initial number, the greater the increase whatever the dose, within the range of 4 to 20 or more grams per day. Consuming a few grams of any of these fructans daily could be sufficient to cause a significant increase in colonic Bifidobacteria. 
USPTO Backgrounds
USPTO Backgrounds