Link:  Pharm/Biotech Resources

Title:  Use of pullulan as a slowly digested carbohydrate

United States Patent:  6,916,796

Issued:  July 12, 2005

Inventors:  Wolf; Bryan W. (Johnstown, OH)

Assignee:  Abbott Laboratories (Abbott Park, IL)

Appl. No.:  167912

Filed:  June 12, 2002

The present invention is directed to the use of pullulan as a slowly digested carbohydrate and to its incorporation into food products, especially beverages and meal replacement products.

SUMMARY OF THE INVENTION

In accordance with the present invention it has been discovered that the literature has mischaracterized pullulan. Pullulan is not an indigestible carbohydrate. In fact, it has been discovered that pullulan is a slowly digested carbohydrate. This means that human enzymes gradually convert pullulan to glucose. The gradual conversion of pullulan to glucose will result in a gradual rise in blood glucose levels in a human.

The discovery of this mischaracterization means that applicants have discovered a number of new uses for pullulan. As a slowly digested carbohydrate, substantial quantities of the pullulan may be incorporated into foods designed for diabetics, thereby providing a blunted glycemic response. The pullulan may be incorporated into meal replacement products, such as beverages and bars. Alternatively, the pullulan may be incorporated into dietetic snack foods designed for diabetics. The pullulan may also be used to control nighttime hypoglycemia in diabetics in need of such therapy.

Pullulan may also be used in foods designed for use in a weight loss program. The gradual release of glucose from the pullulan will produce a feeling of satiety in these individuals. Pullulan may also be used in foods and beverages designed for athletes (i.e. "sport drinks" and "sport bars"). Pullulan will also be beneficial to patients with impaired glucose tolerance. These individuals are often referred to as prediabetics or individuals at risk of developing diabetes. In summary, the pullulan may be used for any application suitable for a slowly digested carbohydrate.

DETAILED DESCRIPTION OF THE INVENTION

As used in this application the following terms have the meanings specified below, unless otherwise noted. The plural and the singular should be considered to have the same meanings, other than the quantity:

As noted above, the prior art has mischaracterized pullulan. The literature contains animal data documenting that pullulan is a nondigestible carbohydrate. As will be demonstrated in the experimental section of this application, this characterization is incorrect. Applicants have demonstrated, in humans, that pullulan is a slowly digested carbohydrate.

Pullulan is a water-soluble, viscous polysaccharide, an alpha-glucan, consisting of glucose units with a relatively simple linear structure, that is, units of three alpha-1,4-linked glucose molecules that are repeatedly polymerized by alpha-1,6 linkages on the terminal glucose. Typical food starches such as corn starch, consist of 27% amylose (alpha 1,4-linked glucose molecules) and 73% amylopectin, which contain both alpha 1,4- and alpha 1,6 glucose linkages. For pullulan, however, the alpha-1,6 linkage serves to cross-link individual short chains resulting in a stair step structure (structure 1). As pullulan has an average molecular weight of 50,000-500,000, n in structure 1 ranges from 300 to 3000. Kimoto et al Food and Chemical Toxicology 35 (1997) 323-329.

Pullulan is elaborated extracellularly by the black yeast, Aureobasidiium pullulans. It is produced by cultivating this same yeast in a medium with sufficient carbon and nitrogen sources and minerals, under aeration. The pullulan is recovered from the culture fluid by centrifugation. It is then typically fractionated with alcohol and purified as is known in the art Kimoto et al, supra. Pullulan is also available commercially from Hayashibara Co. Ltd. of Okayama, Japan.

As noted above, it has been discovered that pullulan is a slowly digested carbohydrate. This effect can be achieved with any of the pullulan molecules having the varying molecular weights described above. The pullulan may be administered as a mixture of compounds having varying molecular weights. If desired, highly purified materials of a single molecular weight may be utilized as well.

The beneficial effects that pullulan has on the blood glucose levels of a diabetic can be achieved in a number of ways. If desired, the pullulan may be administered without any carrier. The pullulan may simply be dissolved in water and consumed by the diabetic. Alternatively, the pullulan may be sprinkled on food, dissolved in coffee, etc. The total daily dose for the diabetic will vary widely, but typically a diabetic will benefit form consuming 1-150 g/day of pullulan.

In a further embodiment, the pullulan may be incorporated into pills, capsules, rapidly dissolved tablets, lozenges, etc. These pharmaceutical dosage forms are especially useful in treating, or preventing, hypoglycemia. The dose for hypoglycemia can vary widely, but will typically range from 1 to 20 g/dose and more typically 5 g/dose. Methods for preparing such dosage forms are well known in the art. The readers attention is directed to the most recent edition of Remingtons Pharmaceutical Sciences for guidance on how to prepare such dosage forms.

While the pullulan may be administered as a single entity, it will typically be incorporated into food products and consumed by the diabetic during their meals or snack. If desired, the diabetic may simply modify the recipe of foods they normally consume. They may simply replace glucose, and other rapidly digested carbohydrates, with an equivalent amount of pullulan. Replacing the rapidly digested sugars with pullulan will significantly reduce the glycemic index of the food. A similar strategy may be utilized by individuals attempting to lose weight because the pullulan will provide for an extended release of glucose and delay the individuals desire to consume additional calories.

While such a strategy will produce foods with a blunted glycemic response, it will also produce a relatively bland diet that many individuals will find objectionable because pullulan is tasteless. Therefore, in a further embodiment, the pullulan will be incorporated into beverages, bars, cookies, etc. that have been specifically designed to enhance the palatability of the pullulan and thereby enhance patient/consumer acceptance.

Typically, the pullulan will be incorporated into meal replacement beverages such as Glucerna®, Ensure®, Choice DM®, Slim Fast®, Pediasure®, Glytrol®, Resource®, Diabetic, etc. The pullulan may also be incorporated into meal replacement bars such as PowerBar®, Glucerna® bars, Choice DM® bars, Ensure® bars, and Boost® bars, etc. Alternatively, the pullulan maybe incorporated into juices, carbonated beverages, bottled water, etc. Methods for producing any of such food products or beverages are well known to those skilled in the art. The following discussion is intended to illustrate such diabetic and weight loss meal replacement products and their preparation.

Most meal replacement products (i.e., bars or liquids) provide calories from fat, carbohydrates, and protein. These products also typically contain vitamins and minerals, because they are intended to be suitable for use as the sole source of nutrition. While these meal replacement products may serve as the sole source of nutrition, they typically don't. Individuals consume these products to replace one or two meals a day, or to provide a healthy snack. The nutritional products of this invention should be construed to to include any of these embodiments.

The amount of these nutritional ingredients can vary widely depending upon the targeted patient population (i.e., diabetics vs. non-diabetics, organoleptic considerations, cultural preferences, use, etc.). As a general nonlimiting guideline however, the meal replacement products of this invention will contain the following relative amounts of protein, fat, and carbohydrate (based upon the relative percentage of total calories):

The novelty of these meal replacement products is the use of pullulan to provide a significant source of carbohydrate calories. As noted above, the carbohydrate will provide from about 25-100% of total calories. Sufficient pullulan should be incorporated into the product so that the pullulan will comprise at least 5 w/w % of the carbohydrate system (when measured on a dry weight basis, i.e. not dissolved in a liquid). More typically, the pulfulan will comprise from about 5 to about 100 w/w% of the carbohydrate system. Alternatively, the pullulan should provide at least 5% of total carbohydrate calories and more typically from 10 to 50%.

The remaining portion of the carbohydrate system (i.e., one or more carbohydrates including pullulan) may be provided by any carbohydrate system suitable for humans, taking into account any relevant dietary restrictions (i.e., if intended for a diabetic). Examples of suitable carbohydrates that may be utilized include starch, modified starch, hydrolyzed corn starch, maltodextrin, glucose polymers, sucrose, corn syrup solids, glucose, fructose, lactose, high fructose corn syrup, fructooligosaccharides, honey, dietary fiber, sugar alcohols (e.g., maltitol).

Specialized carbohydrate blends have been designed for diabetics to help moderate their blood glucose levels. Examples of such carbohydrate blends are described in U.S. Pat. No. 4,921,877 to Cashmere et al., U.S. Pat. No. 5,776,887 to Wibert et al., U.S. Pat. No. 5,292,723 to Audry et al. and U.S. Pat. No. 5,470,839 to Laughlin et al, the contents of which are all incorporated by reference. Any of these carbohydrate blends may be utilized in association with pullulan to further reduce the glycemic index of the product.

If desired, nonabsorbent carbohydrates may be incorporated into the carbohydrate system as well. These nonabsorbent carbohydrate will comprises less than or equal to about 20 wt/wt % of the carbohydrate system, and more typically less than or equal to about 15 wt/wt % of the carbohydrate system. The term "nonabsorbent carbohydrates" refers to a carbohydrate moiety with a degree of polymerization greater than about 20 and/or a molecular weight greater than about 3,600, that is resistant to endogenous digestion in the human upper digestive tract. Nonabsorbent carbohydrates possess many of the characteristics of total dietary fiber. However, they are not quantifiable by the AACC Method 32-07 for fiber and consequently they are not included in total dietary fiber values of the instant invention. Examples of nonabsorbent carbohydrates sources of the instant invention typically include chemically modified starches such as Fibersol, polydextrose and inulin.

Typically, the carbohydrate system will also contain dietary fiber. The quantity of dietary fiber can vary significantly but will typically range from 3 to 20 w/w % of the carbohydrate system (on a dry weight basis). Dietary fiber, as used herein and in the claims, is understood to be all of the components of a food that are not broken down by endogenous enzymes in the human digestive tract to small molecules that are absorbed into the bloodstream. These food components are mostly celluloses, hemicelluloses, pectin, gums, mucilages, and lignins. Fibers differ significantly in their chemical composition and physical structure and therefore their physiological functions.

The properties of fibers (or fiber systems) that impact on physiological function are solubility and fermentability. With regard to solubility, fiber can be divided into soluble and insoluble types based on the fiber's capacity to be solubilized in a buffer solution at a defined pH. Fiber sources differ in the amount of soluble and insoluble fiber they contain. As used herein and in the claims "soluble" and "insoluble" dietary fiber is determined using American Association of Cereal Chemists (AACC) Method 32-07. As used herein and in the claims, "total dietary fiber" or "dietary fiber" is understood to be the sum of the soluble and insoluble fibers determined by AACC Method 32-07 and wherein by weight at least of the fiber source comprises dietary fiber. As used herein and in the claims a "soluble" dietary fiber source is a fiber source in which at least 60% of the dietary fiber is soluble dietary fiber as determined by AACC Method 32-07, and an "insoluble" dietary fiber source is a fiber source in which at least 60% of the total dietary fiber is insoluble dietary fiber as determined by AACC Method 32-07.

Representative of soluble dietary fiber sources are gum arabic, sodium carboxymethyl cellulose, guar gum, citrus pectin, low and high methoxy pectin, oat and barley glucans, carrageenan and psyllium. Numerous commercial sources of soluble dietary fibers are available. For example, gum arabic, carboxymethyl cellulose, guar gum, pectin and the low and high methoxy pectins are available from TIC Gums, Inc. of Belcamp, Md. The oat and barley glucans are available from Mountain Lake Specialty ingredients, Inc. of Omaha, Nebr. Psyllium is available from the Meer Corporation of North Bergen, N.J. while the camageenan is available from FMC Corporation of Philadelphia, Pa.

Representative of the insoluble dietary fibers are oat hull fiber, pea hull fiber, soy hull fiber, soy cotyledon fiber, sugar beet fiber, cellulose and corn bran. Numerous sources for the insoluble dietary fibers are also available. For example, the corn bran is available from Quaker Oats of Chicago, Ill.; oat hull fiber from Canadian Harvest of Cambridge, Minn.; pea hull fiber from Woodstone Foods of Winnipeg, Canada; soy hull fiber and oat hull fiber from The Fibrad Group of LaVale, Md.; soy cotyledon fiber from Protein Technologies International of St. Louis, Mo.; sugar beet fiber from Delta Fiber Foods of Minneapolis, Minn. and cellulose from the James River Corp. of Saddle Brook, N.J.

A more detailed discussion of fibers and their incorporation into formula may be found in U.S. Pat. No. 5,085,883 issued to Garleb et al, which is hereby incorporated by reference.

In addition to fiber, the nutritionals may also contain indigestible oligosaccharides such as fructooligosaccarieds (FOS). Indigestible oligosaccharides are rapidly and extensively fermented to short chain fatty acids by anaerobic microorganisms that inhabit the large bowel. These oligosaccharides are preferential energy sources for most Bifidobacterium species, but are not utilized by potentially pathogenic organisms such as Clostridium perfingens, C. difficile, or E. coli. The term "indigestible oligosaccharide" refers to a small carbohydrate moiety with a degree of polymerization less than or equal to about 20 and/or a molecular weight less than or equal to about 3,600, that is resistant to endogenous digestion in the human upper digestive tract.

The meal replacement products also typically contain a protein source. The protein source may contain intact proteins, hydrolyzed proteins, amino acids, or some combination thereof. The proteins that may be utilized in the nutritional products includes any protein suitable for human consumption. Such proteins are well known by those skilled in the art and can be readily selected when preparing such products. Examples of suitable proteins that may be utilized typically include casein, whey, milk protein, soy, pea, rice, corn, hydrolyzed protein and mixtures thereof. Commercial protein sources are readily available and known to one practicing the art. For example, caseinates, whey, hydrolyzed caseinates, hydrolyzed whey and milk proteins are available from New Zealand Milk Products of Santa Rosa, Calif. Soy and hydrolyzed soy proteins are available from Protein Technologies International of Saint Louis, Mo. Pea protein is available from Feinkost Ingredients Company of Lodi, Ohio. Rice protein is available from California Natural Products of Lathrop, Calif. Corn protein is available from EnerGenetics Inc. of Keokuk, Iowa.

The third component of the nutritional products of this invention is the fat. The fat source for the present invention may be any fat source or blend of fat sources suitable for human consumption. Typically the fat provides the desired levels of saturated, polyunsaturated and monounsaturated fatty adds. One skilled in the art can readily calculate how much of a fat source should be added to the nutritional product in order to deliver the desired levels of saturated, polyunsaturated and monounsaturated fatty acids. Examples of food grade fats are well known in the art and typically include soy oil, olive oil, marine oil, sunflower oil, high oleic sunflower oil, safflower oil, high oleic safflower oil, fractionated coconut oil, cottonseed oil, corn oil, canola oil, palm oil, palm kernel oil, flax seed oil, medium chain triglycerides (MCT) and mixtures thereof. If desired, structured lipids can be incorporated into the nutritional.

Numerous commercial sources for the fats listed above are readily available and known to one practicing the art. For example, soy and canola oils are available from Archer Daniels Midland of Decatur, Ill. Corn, coconut, palm and palm kernel oils are available from Premier Edible Oils Corporation of Portland, Oreg. Fractionated coconut oil is available from Henkel Corporation of LaGrange, Ill. High oleic safflower and high oleic sunflower oils are available from SVO Specialty Products of Eastlake, Ohio. Marine oil is available from Mochida International of Tokyo, Japan. Olive oil is available from Angila Oils of North Humberside, United Kingdom. Sunflower and cottonseed oils are available from Cargil of Minneapolis, Minn. Safflower oil is available from California Oils Corporation of Richmond, Calif. Structured lipids are available from Stepan Oils, having offices in the United States and who can be reached at www.stepan.com.

The nutritional compositions of the invention typically contain vitamins and minerals. Vitamins and minerals are understood to be essential in the daily diet. Those skilled in the art appreciate that minimum requirements have been established for certain vitamins and minerals that are known to be necessary for normal physiological function. Practitioners also understand that appropriate additional amounts of vitamin and mineral ingredients need to be provided to nutritional compositions to compensate for some loss during processing and storage of such compositions. Additionally, the practitioner understands that certain micronutrients may have potential benefit for people with diabetes such as chromium, camitine, taurine and vitamin E and that higher dietary requirements may exist for certain micro nutrients such as ascorbic acid due to higher turnover in people with type 2 diabetes.

An example of the vitamin and mineral system for a complete nutritional product used as a sole source of nutrition typically comprises at least 100% of the RDI for the vitamins A, B₁, B₂, B₆, B₁₂, C, D, E, K, beta-carotene, Biotin, Folic Acid, Pantothenic Acid, Niacin, and Choline; the minerals calcium, magnesium, potassium, sodium, phosphorous, and chloride; the trace minerals iron, zinc, manganese, copper, and iodine; the ultra trace minerals chromium, molybdenum, selenium; and the conditionally essential nutrients minositol, carnitine and taurine in from about 350 Kcal to about 5600 Kcal.

An example of the vitamin and mineral system for a nutritional product used as a nutritional supplement typically comprises at least 25% of the RDI for the vitamins A, B₁, B₂, B₆, B₁₂, C, D, E, K, beta-carotene, Biotin, Folic Acid, Pantothenic Acid, Niacin, and Choline; the minerals calcium, magnesium, potassium, sodium, phosphorous, and chloride; the trace minerals iron, zinc, manganese, copper, and iodine; the ultra trace minerals chromium, molybdenum, selenium; and the conditionally essential nutrients minositol, camitine and taurine in a single serving or from about 50 Kcal to about 800 Kcal.

Artificial sweeteners may also be added to the nutritional product to enhance the organoleptic quality of the formula. Examples of suitable artificial sweeteners include saccharine, aspartame, acesulfame K and sucralose. The nutritional products of the present invention will also desirably include a flavoring and/or color to provide the nutritional products with an appealing appearance and an acceptable taste for oral consumption. Examples of useful flavorings typically include, for example, strawberry, peach, butter pecan, chocolate, banana, raspberry, orange, blueberry and vanilla.

The nutritional products of this invention can be manufactured using techniques well known to those skilled in the art. For liquid meal replacement products, generally speaking, an oil and fiber blend is prepared containing all oils, any emulsifier, fiber and the fat soluble vitamins. Three more slurries (carbohydrate and two protein) are prepared separately by mixing the carbohydrate and minerals together and the protein in water. The slurries are then mixed together with the oil blend. The resulting mixture is homogenized, heat processed, standardized with water soluble vitamins, flavored and the liquid terminally sterilized or dried to produce a powder. Altematively, the homogenized formula may be kept undiluted and filled into appropriate containers as pudding or dried to form powder. The product is then packaged. Typically the package will provide directions for use by the end consumer (i.e., to be consumed by a diabetic, to assist with weight loss, etc.)

Solid nutritional compositions such as bars, cookies, etc. may also be manufactured utilizing techniques known to those skilled in the art. For example, they may be manufactured using cold extrusion technology as is known in the art. To prepare such compositions, typically all of the powdered components will be dry blended together. Such constituents typically. include the proteins, vitamin premixes, certain carbohydrates, etc. The fat soluble components are then blended together and mixed with the powdered premix above. Finally any liquid components are then mixed into the composition, forming a plastic like composition or dough.

The process above is intended to give a plastic mass which can then be shaped, without further physical or chemical changes occurring, by the procedure known as cold forming or extrusion. In this process, the plastic mass is forced at relatively low pressure through a die, which confers the desired shape. The resultant exudate is then cut off at an appropriate position to give products of the desired weight. If desired the solid product is then coated, to enhance palatability, and packaged for distribution. Typically the package will provide directions for use by the end consumer (i.e., to be consumed by a diabetic, to assist with weight loss, etc.)

The solid nutritionals of the instant invention may also be manufactured through a baked application or heated extrusion to produce cereals, cookies, and crackers. One knowledgeable in the arts would be able to select one of the many manufacturing processes available to produce the desired final product.

As noted above, the pullulan may also be incorporated into juices, non-carbonated beverages, carbonated beverages, flavored waters (hereinafter collectively "beverage"), etc. The pullulan will typically comprise from 10 to 100% of the total carbohydrate contact of the beverages. Methods for producing such beverages are well known in the art. The reader's attention is directed to U.S. Pat. Nos. 6,176,980 and 5,792,502, the contents of each which are hereby incorporated by reference. For example, all of the carbohydrates, including the pullulan are dissolved in an appropriate volume of water. Flavors, colors, vitamins, etc. are then optionally added. The mixture is then pasteurized, packaged and stored until shipment.
 

Claim 1 of 18 Claims

1. A meal replacement product comprising:

a) a protein source;

b) a fat source, and;

c) a carbohydrate system, which includes at least one slowly digesting carbohydrate selected from the group consisting of pullulan, in which said pullulan is present in the quantity of at least 5 w/w %, based upon the total carbohydrate present, when measured on a dry weight basis.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.