WO2010075209A1

WO2010075209A1 - Devices for delivering glucose to a subject and methods of making and using thereof

Info

Publication number: WO2010075209A1
Application number: PCT/US2009/068709
Authority: WO
Inventors: Pamela Heyward; Jane Waterman Moss
Original assignee: 15G, Llc
Priority date: 2008-12-22
Filing date: 2009-12-18
Publication date: 2010-07-01

Abstract

Described herein are delivery devices for effectively delivering glucose to a subject with reduced blood glucose levels. The devices are generally composed of a base, glucose, and a protein. The delivery devices can exist in a variety of different forms including gels, capsules, tablets, or gums. The delivery devices are effective not only in raising blood glucose levels in a subject but also maintaining blood glucose levels without the subject experiencing sudden increases in blood glucose levels. The delivery devices are appealing to the subject and, thus, provide an effective way to consistently control and maintain safe blood glucose levels. For example, maintaining safe blood sugar levels is important to subjects who have Diabetes.

Description

DEVICES FOR DELIVERING GLUCOSE TO A SUBJECT AND METHODS OF MAKING AND USING THEREOF

CROSS REFERENCE TO RELATED APPLICATION This application claims priority upon U.S. provisional application Serial

No. 61/139,645, filed December 22, 2008. This application is hereby incorporated by reference in its entirety for all of its teachings.

BACKGROUND

Hypoglycemia is a condition where blood glucose levels in a subject are abnormally low. Hypoglycemia may occur when plasma insulin levels rise to higher than normal levels, which results in a decrease in blood glucose levels and overall energy. Mild to moderate hypoglycemia can result in symptoms that include hunger, nervousness, shakiness, perspiration, light-headedness, dizziness, sleepiness, anxiety, weakness, difficulty in speaking , nightmares, irritability, slurred speech, confusion, hunger, lightheadedness, irrational activity, headache, personality change, nausea, crying, sluggishness, pale skin color, clumsiness or jerkiness, an inability to concentrate, a tingling sensation around the mouth, tiredness and even seizure. If mild or moderate hypoglycemia is not treated promptly, it can develop into severe hypoglycemia. Severe hypoglycemia occurs when blood glucose levels decrease and remain at a low level for too long. Severe hypoglycemia, a condition also known as insulin shock, can cause the brain to become deprived of sufficient energy to function properly, which can result in a loss of consciousness, irrational activity, seizure, coma or death.

In general, treatment for hypoglycemia involves the administration of glucose to the subject in order to raise the subject's blood glucose level. The source of glucose can vary. For example, the subject can ingest a solid food or beverage containing a number of different sugars including glucose. Although this approach is simple in theory, it may be difficult to administer a sufficient amount of glucose to a subject in order to raise the subject's blood glucose level. This may be especially true for children, where the child may not be interested, for a variety of reasons, in ingesting food when they need it most. Additionally, the child may not, on a consistent basis, ingest a sufficient amount of glucose to maintain sufficient blood glucose levels. Alternatively, ingesting too much glucose can cause a sudden increase in blood glucose levels, which can cause undesirable effects on the subject as well. This condition is known as hyperglycemia. The American Diabetes Association (ADA) recommends ingesting 15 grams of glucose to raise low blood glucose levels. The ADA also comments on the sustainability of glucose levels and, for example, recommends that a drink like milk is better than juice as a source of glucose, because the milk contains lactose, a sugar, fat and protein, which will keep blood glucose levels steady over time.

Another related challenge for diabetics when controlling glucose levels is the need to conduct carbohydrate counting (a.k.a. carb counting), which is a laborious method used to measure carbohydrate intake from meals and snacks. Carb counting requires diabetics to use fast acting insulin to match or cover the effect of raised blood glucose levels due to carbohydrate intake. A related issue is the risk of ingesting unnecessary carbohydrates to treat hypoglycemia. This added intake can lead to weight gain, which has adverse effects in controlling blood glucose levels and diabetes management in general. Conversely, caloric restriction and weight loss have been shown to improve insulin resistance, prevent or delay the onset of diabetes, maintain normal glycemic levels, and improve Al C concentrations, also known as Hemoglobin AIc (HbAIc).

People who suffer from hypoglycemia and related Type 1 and Type 2 Diabetes need a convenient and efficient way to administer glucose to a subject to treat low blood glucose levels and help maintain safe blood sugar levels. It would be desirable to have a delivery device that is acceptable to all subjects including children that consistently delivers a desirable amount of glucose to the subject. The delivery device should also have a pleasant taste and texture, and be able to withstand different temperature ranges, so that the subject is willing to ingest the device with the glucose on a routine basis. The delivery devices described herein address these needs.

SUMMARY

Described herein are delivery devices for effectively delivering glucose to a subject with reduced blood glucose levels. The devices are generally composed of a base, glucose, and a protein. The delivery devices can exist in a variety of different forms including gels, capsules, tablets, or gums. The delivery devices are effective not only in raising blood glucose levels in a subject but also maintaining an acceptable blood glucose level without the subject experiencing sudden increases in blood glucose levels, known as "spiking". Spiking is a condition some people with Diabetes have experienced. The delivery devices are appealing to the subject and, thus, provide an effective way to consistently control and maintain safe blood glucose levels.

The advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the aspects described below. The advantages described below will be realized and attained by means of the elements and combinations described herein. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive. DETAILED DESCRIPTION

Before the present compounds, compositions, articles, devices, and/or methods are disclosed and described, it is to be understood that the aspects described below are not limited to specific compounds, synthetic methods, or uses and as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings:

It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a flavorant" includes mixtures of two or more such flavorants, and the like.

"Optional" or "optionally" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, the phrase "optional emulsifier" means that the delivery device may or may not contain the emulsifier.

The term "subject" as used herein is any mammal experiencing below- normal blood glucose levels that is in need of raising and maintaining normal blood glucose levels. The term "subject" also includes any mammal that has normal blood glucose levels but is in need of maintaining normal blood glucose levels.

Described herein are delivery devices for delivering glucose to a subject in order to raise and maintain the subject's blood glucose level. The delivery devices are generally composed of a base, glucose, and a protein. Each component of the delivery device is described below. The device can assume a variety of different shapes and forms. For example, the device can be a gel, a capsule, a tablet, a gum, or any other suitable device that can be ingested orally. The design of the device can be tailored to a particular group of subjects. For example, if the subject is a child, the device can be formulated as a candy (e.g., a gummy bear).

The selection of the base will vary depending upon the application of the device. For example, if the device is a chewing gum, a variety of different gum bases typically used to make gums can be used to produce the gums of the present invention. In one aspect, the gum base includes a natural based material such as, for example, chicle, natural rubber, crown gum, nispero, rosidinha, jelutong, perillo, niger gutta, tunu, balata, guttapercha, lechi capsi, sorva, gutta kay, or any combination thereof. In other aspects, the gum base can be a synthetic based material such as, for example, styrene-butadiene copolymers (SBR), polyisobutylene, isobutylene-isoprene copolymers, polyethylene, polyvinyl acetate and the like, or any combination thereof. In other aspects, the base can be polybutuylmethacrylate/acrylic acid copolymers, polyvinylacetate/vinylalcohol copolymers, microcrystalline celluylose, sodium carboxymethyl cellulose, hydroxylpropylmethyl cellulose, crosslinked cellulose acetate phthalate, crosslinked hydroxyl methyl cellulose polymers, zein, crosslinked polyvinyl pyrrolidone, polymethylmethacrylate/acrylic acid copolymers, copolymers of lactic acid, polyhydroxyalkanoates, plasticized ethylcellulose, polyvinyl acetatephthalate and combinations thereof. It is also contemplated that the gum base can include a mixture of a natural based material and a synthetic based material. In certain aspects, the base has substantially little to no digestible carbohydrates, which can help control the amount of glucose that is administered to the subject. The amount of base used to make the device will vary depending upon the design of the delivery device. In one aspect, the amount of base is from 1% to 50%, 10% to 45%, 15% to 40%, 20% to 40%, or 25% to 35% by weight of the device. Other properties, such as the molecular weight of the polymer used as the base, can vary. In one aspect, the molecular weight of the polymer can have an average molecular weight of at least about 200,000. In other aspects, the molecular weight is from about 200,000 to about 2,000,000.

The devices described herein include one or more proteins. Not wishing to be bound by theory, it is believed that the protein maintains blood glucose levels upon administration of the glucose via the delivery device. Upon administration of the delivery device, the subject's blood glucose level does not rise dramatically then drop significantly. Thus, the use of the delivery devices described herein increases and maintains healthy blood glucose levels upon ingestion of the device. The protein can be derived or obtained from a variety of sources. In one aspect, the protein is a grain protein derived from corn, wheat, barley, rice, oat, soya sorghum proteins, their fractions thereof, or any combination thereof. Examples of such fractions include gluten or prolamines (e.g. as zein, glutenin and gliadin). In other aspects, the protein is an animal protein such as, for example, collagen, gelatin, egg albumin (ovalbumin), lactalbumin, casein, sodium caseinate, whey, a milk isolate, a gluten-free protein, a gluten-free animal source protein, or any combination thereof. In a further aspect, the protein comprises a vegetable protein, wherein the vegetable protein comprises pea, bean, soy, nut, seed, yeast, algal or any other vegetable source (eg. artichokes, beets, broccoli, brussels sprouts, cabbage, cauliflower, cucumbers, eggplant, green peas, green pepper, kale, Lettuce, mushrooms, mustard green, onions, potatoes, spinach, tomatoes, turnip greens, watercress, yams, zucchini), or any combination thereof. The amount of protein used in the device can vary depending upon the amount of glucose present in the device. In the case when the device is a chewing gum, the amount of protein can vary such that the gum possesses more or less nonstick properties. If too much protein is added, the gum does not have a desirable texture or feel when ingested. In one aspect, the amount of protein is from 1% to 15%, 2% to 15%, 3% to 15%, 4% to 15%, or 5% to 15% by weight of the gum. In another aspect, the weight ratio of protein/glucose is from about 1:1 to 1:5, 1:2 to 1:5, or 1:3 to 1:5. Here, the amount of protein and glucose is balanced to incorporate the highest amount of glucose in the device yet not compromise the overall texture and feel of the gum. Turning to the glucose component of the delivery device, the source and amount of glucose can vary depending upon the design of the delivery device. In certain aspects, the source of the glucose can be pure glucose powder or syrup, where the source is 100% glucose. In other aspects, the source of glucose can be a mixture of sugars that includes glucose. Examples of this include, but are not limited to, liquid glucose, powdered glucose, corn syrup, and high fructose corn syrup (HFCS) . HFCS is a group of corn syrups that have been enzymatically modified to increase the fructose content. Examples of HFCS include, but are not limited to, HFCS 55 (contains 55% fructose and 45% glucose) and HFCS 42 (contains 42% fructose and 58% glucose). Alternatively, pure glucose can be mixed with high fructose corn syrup to produce varying amounts of glucose. In other aspects, the source of glucose can include a sugar that is readily converted to glucose upon ingestion.

The amount of glucose present in the device can vary depending upon the size and formulation of the device. As will be described below, in order to treat subjects with reduced blood glucose levels, it is desirable to administer at least 15 grams of glucose to the subject per serving. The number or pieces of the device per serving can vary depending upon the device. In one aspect, the device contains from 3 g to 20 g glucose per individual device (i.e., per piece). Thus, for example, if 15 grams were to be administered to the subject in two pieces of gum, each piece of gum could contain about 7.0 g to 8.0 g of glucose. Similarly, if three pieces of gum were to be administered, each piece of gum could have about 4.5 g to 5.5 g of glucose per piece. In other aspects, the device can be a single entity such as a tablet or capsule that contains about 10 g to 20 g.

The delivery devices described herein can include additional components that help increase and maintain healthy blood glucose levels. For example, cinnamon can be added to help increase insulin activity in the subject. Cinnamon can also be used as a flavorant. Other flavorants that can be used alone or in combination with cinnamon include, but are not limited to, natural and artificial flavors. Examples of flavorants include, but are not limited to, (A) flavor oils such as spearmint, oil of wintergreen (methyl salicylate), peppermint (menthol), clove, bay, anise, eucalyptus, thyme, cedar leaf, oil of nutmeg, allspice, oil of sage, mace, oil of bitter almonds, and cassia oil; (B) artificial, natural and synthetic fruit flavors such as vanilla, and citrus oils including lemon, orange, lime, grapefruit, and fruit essences including apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot and so forth; (C) aldehydes and esters such as acetaldehyde, benzaldehyde, anisic aldehyde, cinnamic aldehyde, citral, neral, decanal, ethyl vanillin, heliotrope, piperonal, vanillin, alpha-amyl cinnamaldehyde, butyraldehyde, valeraldehyde, citronellal, decanal, dihydrocarvyl acetate, eugenyl formate, aldehyde C-8, aldehyde C-9, aldehyde C-12, 2-ethyl butyraldehyde, hexenal, tolyl aldehyde, veratraldehyde, 2,6-dimethyl-5-heptenal, 2,6- dimethyloctanal, 2-dodecenal, p-methylanisol, and so forth. Generally any flavoring or food additive such as those described in Chemicals Used in Food Processing, publication 1274, pages 63-258, by the National Academy of Sciences, incorporated herein by reference, may be used. Other ingredients which may be used as the flavorant include acids such as citric, tartaric, malic and the like acidulants. The effective amount of flavorant added to the device varies significantly depending on the nature and strength of the flavorant. In one aspect, the flavorant is from 0.0001% to 10% by weight of the device.

In one aspect, the flavorant is cinnamon. In addition to providing an appealing flavor to the device, cinnamon can increase glucose metabolism in a subject. Cinnamon contains a variety of different chalcones, which are a type of polyphenol or flavonoid. For example, methyl hydroxy chalcone polymer or "MCHP", which is present in cinnamon, has been shown to significantly enhance glucose metabolism. Therefore, cinnamon can additionally act as an insulin booster. In other aspects, the device can include an absorption enhancer. In general, the absorption enhancer is a compound that enhances the ability of the subject to absorb glucose. For example, the absorption enhancer can facilitate the absorption of glucose by a mucosal membrane in the mouth (e.g., gums, lips, etc.). Examples of absorption enhancers useful herein include, but are not limited to, lecithin, hyaluronic acid, glycolic acid, lactic acid, chamomile extract, cucumber extract, oleic acid, linoleic acid, linolenic acid, monoolein, monooleates, monolaurates, borage oil, evening primrose oil, menthol, trihydroxy oxo cholanyl glycine, glycerin, poly glycerin, lysine, polylysine, triolein, polyoxyethylene ethers, polidocanol alkyl ethers, chenodeoxycholate, deoxycholate, alkali metal salicylate, pharmaceutically acceptable edetate, and pharmaceutically acceptable salts and analogues thereof, or any combination thereof. The effective amount of an absorption enhancer will vary depending on the nature of the absorption enhancer. In one aspect, the amount of absorption enhancer is from 1% to 4% by weight of the device. The devices described herein can include additional components useful in formulating the device. Examples of organic plasticizers useful herein include, but are not limited to, phthalate derivatives such as dimethyl, diethyl and dibutyl phthalate; polyethylene glycols with molecular weights preferably from about 200 to 6,000; glycerol; glycols such as polypropylene, propylene, polyethylene and ethylene glycol; citric esters such as tributyl, triethyl and triacetyl citrates; surfactants such as sodium dodecyl sulfate, polyoxymethylene (20) sorbitan and polyoxyethylene (20) sorbitan monooleate, blended with water; alcohols such as ethanol and isopropyl alcohol; organic acids such as acetic and lactic acids and their lower alkyl esters; bulk sweeteners such as sorbitol, mannitol, xylitol and lycasin; fats/oils such as vegetable oil, seed oil and castor oil; acetylated monoglyceride; triacetin; sucrose esters; traditional flavor oils; or mixtures thereof. Other examples include polyols such propylene glycol, polypropylene glycol, ethylene glycol and polyethylene glycol, and organic acids especially lactic and acetic acid, and their corresponding esters. In another aspect, the device may include one or more softeners. Examples of softeners useful herein include, but are not limited to, tallow, hydrogenated tallow, hydrogenated and partially hydrogenated vegetable oils, cocoa butter, glyceryl monostearate, glyceryl monolaurate, glyceryl monooleate, polysorbate 60, polysorbate 65, tween 65, tween 80, glycerol triacetate, lecithin, mono-, di-, and tri-glycerides, acetylated monoglycerides fatty acids and combination thereof. Preferred fatty acids include stearic, palmitic, oleic and linoleic acids.

The devices herein can include one or more pigments for color. Examples of pigments useful in the devices described herein include, but are not limited to, titanium dioxide, natural food colors and dyes suitable for food, drug and cosmetic applications, known as F.D.&C. dyes and lakes. A recitation of all F.D.&C. colorants and their corresponding chemical structures may be found in the Kirk- Othmer Encyclopedia of Chemical Technology, 3.sup.rd Edition, in Volume 5 at page 857-884, which is incorporated herein by reference.

In addition to glucose, the delivery devices can contain one or more sugar or non-sugar bulking agents. Examples of sugar based agents include monosaccharides, disaccharides and polysaccharides such as xylose, ribulose, glucose (dextrose), mannose, galactose, fructose (levulose) sucrose (sugar), maltose, invert sugar, partially hydrolyzed starch and corn syrup solids, and mixtures thereof. Suitable non-sugar bulking agents include sugar alcohol bulking agents such as sorbitol, xylitiol, mannitol, galactitol, maltitol, and mixtures thereof, isomalt, maltodextrins; hydrogenated starch hydrolysates; hydrogenated hexoses; hydrogenated disaccharides; and the like, and mixtures thereof.

In certain aspects, when the device is a gum, one or more waxes can be present in the device to improve the elasticity of the gum base. Waxes can provide a soft or firm chew, influence the flavor release and provide bulkiness and smoothness to the gum base. Examples of waxes include paraffin, microcrystalline waxes, polyethylene wax, paraffin wax, beeswax, carnauba wax, microcrystalline wax, carnauba wax, candellila wax, rice bran wax, esparto wax, flax wax, sugarcane wax, and synthetic waxes. Elastomer solvents can also be present in the gum base composition, wherein they act in softening or plasticising the base. Chewing gum base elastomer solvents include pentaerythritol ester of wood rosin, glycerol ester of polymerised rosin, partially hydrogenated methyl ester of rosin, and the like.

When the device is a gum, the gum base also may include emulsifiers which aid in dispersing the immiscible components of the gum base into a single stable system. Emulsifiers useful herein include, but are not limited to, glyceryl monostearate, lecithin, fatty acid monoglycerides, diglycerides, propylene glycol monostearate, and the like, and mixtures thereof.

In one aspect, the delivery device is a gum, and the gum comprises a gum base, glucose, a protein, glycerin, and cinnamon. In another aspect, the delivery device is a gum comprising the following components: a base comprising chicle, glucose, a protein comprising whey protein, glycerin, and cinnamon. In a further aspect, the device is a gum comprising the following components: a base comprising chicle, glucose, a protein comprising whey protein, glycerin, cinnamon, and corn syrup.

Methods for making the delivery devices described herein generally involve admixing the base, glucose, and protein for a sufficient time and temperature to intimately mix the components followed by producing the delivery device in a desired shape. In one aspect, a chewing gum can be prepared by the following method:

(a) mixing the protein, the glucose and cinnamon to produce a first mixture;

(b) mixing the first mixture with heated corn syrup to produce a second mixture;

(c) melting the base;

(d) admixing the second mixture with the melted base for a sufficient time and temperature to produce a third mixture; and

(e) molding the fourth mixture into a desired shape. More details for producing the devices herein such as chewing gums are provided in the Examples.

In one aspect, the delivery device can be prepared by compressing the ingredients (wet and/or dry) to produce a compressed article. For example, the compressed article can be produced by the method comprising: a. premixing the protein, glucose, cinnamon, the base to produce a mixture, b. placing the mixture in a mold, c. applying pressure for a sufficient time and temperature to produce the delivery device, d. releasing the delivery device from the mold; and e. coating the delivery device by a panning process.

Techniques for producing compressed articles such as, for example, chewing gum, can be used herein. In general, the ingredients are mixed so that they are evenly dispersed throughout the mixture, then the mixture is placed in a mold having a desired shape and dimensions. A sufficient amount of pressure is applied to the mold. The amount of pressure can be readily determined through routine experimentation. After applying pressure, the molded device is removed, and can be subsequently processed. For example, the molded device can be coated using techniques known in the art (e.g., a panning or shelling process).

The delivery devices described herein are useful in increasing and maintaining blood glucose levels in subjects that are suffering from hypoglycemia. The devices described herein are an especially attractive source of glucose to children, where it is difficult to consistently administer glucose. The devices can easily administer at least 15 grams of glucose to a subject, which is the ADA recommended dose of glucose for treating hypoglycemia. The devices herein generally contain little to no fat, which helps facilitate the circulation of glucose through the blood stream. Upon ingestion of the device, blood glucose levels can increase immediately. Additionally, the blood glucose levels can be maintained at acceptable levels up to several hours. Results will depend upon the individual as well as his/her activity level and food intake. The delivery devices can be useful as snacks between meals, where there is a tendency for blood glucose levels to drop in the subject. EXAMPLES

The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, and methods described and claimed herein are made and evaluated, and are intended to be purely exemplary and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. There are numerous variations and combinations of reaction conditions, e.g., component concentrations, desired solvents, solvent mixtures, temperatures, pressures and other reaction ranges and conditions that can be used to optimize the product purity and yield obtained from the described process.

The following procedure was used to make a gum for delivering glucose to a subject. 1. Weigh out all ingredients (50 grams chicle base; 66 grams high fructose corn syrup (HFCS); 14 grams whey protein; 4 grams cinnamon powder; 20 grams glucose powder).

2. Heat the corn syrup to approximately 140 ⁰F.

3. Add whey protein and the cinnamon powder together in a container and mix.

4. Add dry ingredients (whey and cinnamon powder) to the corn syrup and mix to evenly distribute.

5. In a separate container, heat the chicle gum base till the pellets are completely melted.

6. Add the corn syrup mixture to the Chicle gum base and combine quickly by stirring to yield a smooth paste.

7. Dust a flat surface with powdered sugar and spoon gum paste onto it.

8. Knead gum in a rolling, folding motion, to make a smooth product.

9. Roll tol inch thickness and cut into weighed squares.

A breakdown of the each component in the gum is provided in Table 1.

Table 1

Various modifications and variations can be made to the compounds, compositions and methods described herein. Other aspects of the compounds, compositions and methods described herein will be apparent from consideration of the specification and practice of the compounds, compositions and methods disclosed herein. It is intended that the specification and examples be considered as exemplary.

Claims

What is claimed:

1. A digestible delivery device comprising a base, glucose, and a protein.

2. The delivery device of claim 1, wherein the device comprises a gel, a capsule, a tablet, or a gum.

3. The delivery device of claim 1, wherein the device is a chewing gum.

4. The delivery device of claim 1, wherein the device comprises glucose in the amount of 1 g to 15 g per individual device.

5. The delivery device of claim 1, wherein the device comprises glucose in the amount of 3 g to 10 g per individual device.

6. The delivery device of claim 1, wherein the device comprises glucose in the amount of 4.5 g to 5.5 g per individual device.

7. The delivery device of claim 1, wherein the device comprises glucose in the amount of 7.0 g to 8.0 g per individual device.

8. The delivery device of claim 1, wherein the device comprises glucose in the amount of 14.5 g to 20.0 g per individual device.

9. The delivery device of claim 1, wherein the glucose comprises pure glucose or a mixture of glucose and one or more additional sugars.

10. The delivery device of claim 1, wherein the glucose is present in high fructose corn syrup.

11. The delivery device of claim 1 , wherein the protein comprises a grain protein, and the grain protein comprises corn, wheat, barley, rice, oat, soya sorghum proteins, their fractions thereof, or any combination thereof.

12. The delivery device of claim 1, wherein the protein comprises an animal protein, and the animal protein comprises collagen, gelatin, egg albumin (ovalbumin), lactalbumin, casein, sodium caseinate, whey, a milk isolate, a gluten-free protein, a gluten-free animal source protein, or any combination thereof.

13. The delivery device of claim 1, wherein the protein comprises a vegetable protein, wherein the vegetable protein comprises pea, bean, soy, nut, seed, yeast, algal or a vegetable source selected from the group consisting of artichokes, beets, broccoli, brussels sprouts, cabbage, cauliflower, cucumbers, eggplant, green peas, green pepper, kale, lettuce, mushrooms, mustard green, onions, potatoes, spinach, tomatoes, turnip greens, watercress, yams, and zucchini, or any combination thereof.

14. The delivery device of claim 1, wherein the amount of protein is from 1% to 15% by weight of the gum.

15. The delivery device of claim 1, wherein the weight ratio of protein/glucose is from about 1:1 to 1:5.

16. The delivery device of claim 1, wherein the device comprises a gum and the base comprises a gum base.

17. The delivery device of claim 16, wherein the gum base comprises a natural based material.

18. The delivery device of claim 17, wherein the natural based material comprises chicle, natural rubber, crown gum, nispero, rosidinha, jelutong, perillo, niger gutta, tunu, balata, guttapercha, lechi capsi, sorva, gutta kay, or any combination thereof.

19. The delivery device of claim 16, wherein the gum base comprises a synthetic based material.

20. The delivery device of claim 19, wherein the synthetic based material comprises styrene-butadiene copolymers (SBR), polyisobutylene, isobutylene-isoprene copolymers, polyethylene, polyvinyl acetate and the like, or any combination thereof.

21. The delivery device of claim 16, wherein the gum base is from 1% to 50% by weight of the gum.

22. The delivery device of claim 16, wherein the gum base comprises substantially no digestible carbohydrates.

23. The delivery device of claim 1, wherein the device comprises no fat.

24. The delivery device of claim 1, wherein the device further comprises a bulking agent, a wax, an elastomer solvent, an emulsifier, a plasticizer, a softener, a pigment, or any combination thereof.

25. The delivery device of claim 1, wherein device further comprises one or more flavorants.

26. The delivery device of claim 25, wherein the flavorant comprises cinnamon.

27. The delivery device of claim 25, wherein the flavorant is from 0.0001% to 10% by weight of the device.

28. The delivery device of claim 1, wherein device further comprises an absorption enhancer.

29. The delivery device of claim 28, wherein the absorption enhancer comprises lecithin, hyaluronic acid, glycolic acid, lactic acid, chamomile extract, cucumber extract, oleic acid, linoleic acid, linolenic acid, monoolein, monooleates, monolaurates, borage oil, evening primrose oil, menthol, trihydroxy oxo cholanyl glycine, glycerin, polyglycerin, lysine, polylysine, triolein, polyoxyethylene ethers, polidocanol alkyl ethers, chenodeoxycholate, deoxycholate, alkali metal salicylate, pharmaceutically acceptable edetate, and pharmaceutically acceptable salts and analogues thereof, or any combination thereof.

30. The delivery device of claim 1, wherein the device is a gum, and the gum comprises a gum base, glucose, a protein, glycerin, and cinnamon.

31. The delivery device of claim 1, wherein the device is a gum comprising the following components: a base comprising chicle, glucose, a protein comprising whey protein, glycerin, and cinnamon.

32. The delivery device of claim 1, wherein the device is a gum comprising the following components: a base comprising chicle, glucose, a protein comprising whey protein, glycerin, cinnamon, and corn syrup.

33. The delivery device of claim 1, wherein the device is a compressed article.

34. The delivery device of claim 1, wherein the device is a non-compressed article.

35. A method for making the device of claim 1, comprising admixing the base, glucose, and protein for a sufficient time and temperature to produce the delivery device.

36. The method of claim 35, wherein the method comprises:

(a) mixing the protein, the glucose and cinnamon to produce a first mixture;

(b) mixing the first mixture with heated corn syrup to produce a second mixture; (c) melting the base;

(e) molding the fourth mixture into a desired shape.

37. The method of claim 35, wherein the glucose comprises powdered glucose.

38. A method of making the device of claim 1, comprising compressing a mixture of a base, glucose, and a protein to produce the delivery device.

39. The method of claim 38, wherein the method comprises: a. premixing the protein, glucose, cinnamon, the base to produce a mixture, b. placing the mixture in a mold, c. applying pressure for a sufficient time and temperature to produce the delivery device, d. releasing the delivery device from the mold; and e. coating the delivery device by a panning process.

40. A method for increasing blood glucose levels in a subject comprising orally administering the device in any of claims 1-34 to the subject, wherein the total amount of glucose administered per dose is at least 15 grams.

41. A method for treating hypoglycemia in a subject by orally administering the device in any of claims 1-34 to the subject, wherein the total amount of glucose administered per dose is at least 15 grams.

42. The method of claims 40 or 41 , wherein the total amount of glucose administered per dose is 15 to 20 grams.

43. The method of claims 40 or 41, wherein the device comprises a chewing gum, wherein two or more pieces of gum are administered to the subject.