Patent Application
20070280997
In accordance with the present invention, it has been found that selective carbohydrates and protein in a specific weight ratio of from about 1.5:1 to 2:1, combined with a specific amino acid component, form a unique essential composition that is useful for retarding muscle atrophy and loss of strength resulting from extended periods of inactivity, such as would be necessitated by surgery, injury or illness. The subject essential compositions are unique in that they maximize and extend the synthesis of protein thereby retarding the loss of muscle strength and tone and preventing atrophy, even in the absence of stimulation by exercise. The subject compositions are advantageous in that, unlike conventional preparations intended to aid muscle recovery from exercise, they are specifically formulated to aid and enhance muscle recovery where the patient is incapable of exercising the affected muscles.
While the subject compositions are in some ways similar to the compositions disclosed in U.S. Pat. No. 6,051,236, as well as in certain compositions disclosed in the literature as discussed above, they differ in critical ways that make them uniquely advantageous for use by individuals who suffer from, or have the potential to undergo, muscle weakness and atrophy as the result of extended inactivity due to surgery, injury, illness or similar causes. It has unexpectedly been found that a specific weight ratio of from about 1.5:1 to 2:1 carbohydrate to protein, in combination with a specific amino acid component described below, renders the subject essential compositions particularly advantageous for treating or preventing muscle weakness and/or atrophy resulting from extended inactivity.
A major difference between the biochemical state of muscles post-exercise versus that resulting from a period of forced inactivity is related to the insulin responsiveness of the muscle cells. Muscle cells post-exercise have a heightened responsiveness to insulin, which is not found in muscle cells following a period of forced inactivity. As a result of this essential finding, the compositions of the present invention are formulated to include specific nutrients that stimulate and maintain insulin levels to enhance muscle anabolic activity.
The carbohydrate component of the essential compositions of the present invention consists of at least two sugars selected from the group consisting of sucrose, glucose, fructose and maltodextrin. The carbohydrate component improves the palatability of the subject compositions. This is advantageous in terms of patient compliance since, typically, it may be necessary for an individual to take the subject compositions for a number of weeks, for example, where a member is immobilized in a cast, or where major surgery forces inactivity. Optimally, the two or more sugars making up the carbohydrate component are present in approximately equal quantities although they may be present in a weight ratio of up to about 10 to 1. Where more than two sugars are present, it is preferred that they be in equal quantities. A preferred carbohydrate component is a mixture of approximately equal quantities of glucose and sucrose. The essential composition according to the present invention, on a dry weight basis, contains from about 35% to about 70%, preferably from about 45% to about 66% by weight of the carbohydrate component.
The protein component of the essential compositions of the present invention comprises a combination of whey and a casein proteins. The whey protein can be in any of the commercially available forms, such as the concentrate, hydrolysate or isolate. Likewise, casein may be in commercially available form, such as calcium caseinate. The relative proportion of whey protein to casein should preferably be a weight ratio of about 3:1 and should not exceed about 9:1. This combination of proteins is optimum in providing an extended level of protein synthetic activity in that the whey protein produces a fast-acting effect, whereas the caseinate produces a more sustained effect. While whey protein is preferred in the subject compositions, other fast-acting proteins, such as soy protein, may be used, for example, where the patient has demonstrated an allergic reaction to milk proteins. The total protein concentration in the essential composition of the present invention is from about 25% to 35%, preferably from about 30% to 33% by weight, based on the dry composition.
The specific carbohydrate to protein ratio of about 1.5:1 to 2:1 in the essential compositions of the subject invention is necessary to increase blood amino acid levels, thereby stimulating insulin production to maintain a high level of glucose and amino acids into the muscle cells and stimulate muscle glycogen synthesis. Increased blood amino acid levels independently increase protein synthesis by activating protein translation, an essential step in the manufacture of protein. These anabolic activities strengthen the muscles against weakening and atrophy that would occur were the level of these activities to drop as a result of inactivity over extended periods of time. In contrast, a preparation to be taken following exercise will ideally contain a higher ratio of carbohydrate to protein because the cells are in an insulin responsive state.
An essential difference in the use of the subject compositions to enhance muscle recovery and prevent or minimize muscle atrophy following inactivity for an extended period of time versus a preparation used after exercise is the lower carbohydrate to protein content of the subject compositions. Consuming higher levels of carbohydrate during a period of forced inactivity could result in weight gain since the individual in the large majority of instances will not be able to partake in the physical activity and exercise necessary to burn off the carbohydrate calories.
The subject essential compositions additionally contain an amino acid component consisting of leucine and, optimally, arginine. The branched-chain amino acid leucine compliments the protein-carbohydrate components because it is a potent activator of muscle growth. It serves not only as a building block for muscle proteins, but helps amplify muscle protein synthesis via three mechanisms. First, leucine increases blood insulin levels by stimulating the release of insulin from the pancreas. Second, it works in cooperation with insulin to initiate protein synthesis, and third, leucine increases protein synthesis by stimulating translation mechanisms. Leucine is present in the compositions of the invention in from about 6% to 9% by weight, preferably from about 7% to 8% by weight, based on the dry weight of the essential composition
The addition of arginine provides two important benefits to the subject compositions. Arginine is an effective stimulator of insulin release. The inclusion of arginine provides a second mechanism to create the necessary insulin levels that drive protein synthesis and thus enables the carbohydrate content to be further reduced thereby resulting in a calorically efficient preparation. Individuals who undergo periods of forced inactivity following orthopedic surgery or injury expend less calories per day. Reducing the total amount of calories in the subject preparations also decreases the potential conversion of unused calories into unwanted weight gain. Furthermore, a natural consequence of forced inactivity is a reduced blood flow to muscles, particularly where a limb is immobilized, as in a cast. When blood flow is reduced, there is a decrease in the amount of nutrients received by muscle cells and, therefore, a decrease in muscle synthetic activity. Arginine increases the flow of blood to muscle cells by stimulating nitric oxide mechanisms. This is an important benefit to individuals who are undergoing forced inactivity following injury, illness or surgery. Arginine is optimally present in the essential compositions of the invention in from about 3% to 9% by weight, preferably about 7% to 8% by weight, based on the dry composition.
Preparations containing the essential compositions on the subject invention for consumption may be in the form of a dry powder that can be utilized by an individual in need thereof in a number of ways, or in a prepared liquid drink or solid form, such as an nutrient bar. In either instance, such preparations will contain conventional flavoring and sweetening agents and suitable coloring agents to compliment the flavor imparted thereto, for example a yellow color would be utilized with a banana flavor and the like. The preparations may also contain one or more of emulsifiers, fillers, binders, wetting agents and suitable liquid or solid vehicles for the administration of foods. For incorporation into a liquid preparation to form a drink, there may be included emulsifiers, including but not limited to, lecithin and phosphatidyl choline derivatives, acacia, or veegum and one or more surfactants, particularly non-ionic surface active agents, for example the Tween series.
The preparations containing the subject essential compositions may likewise include coloring agents, or pigments, such as FD&C or D&C approved lakes and dyes, iron oxide and titanium dioxide and artificial sweeteners, such as aspartame, sodium cyclamate and sodium saccharinate. The flavoring component may include, without intended limitation, water soluble, natural or artificial extracts of apple, banana, cherry, cinnamon, cranberry, grape, honeydew, kiwi, lemon, lime, orange, peach, peppermint, pineapple, raspberry tangerine, watermelon, wild cherry and the like.
Preparations containing the subject essential compositions in powder form are preferably formulated to be combined with a food or foods, or more preferably, a suitable liquid such as water or a juice. It is also contemplated that such preparations may be formulated pre-mixed with a liquid or solid vehicle suitable for the administration of foods, such as a prepared drink, or in a bar, such as commercial power bars. Regardless, it is contemplated such preparations will comprise from about 15% to about 80% by weight of the essential composition as described above with the remainder being conventional excipient materials recognized as being useful in such preparations, also as described above. The amount and selection of the type of excipients would depend on the desired final form of the preparation and are considered to be within the purview of a person skilled in the relevant compounding or formulating arts.
The essential compositions of the present invention are preferably administered in a plurality of doses over the course of a day to achieve maximum benefit, for example, with meals. It is considered to be of greater benefit in the prevention of loss of muscle strength and atrophy that administration of the subject compositions be at intervals over a day rather than a larger dosage given in a single administration. The subject composition are equally important for their preventative capacity where there is the potential for muscle atrophy as for their capacity to neutralize or reverse to some extent the process of loss of muscle strength or atrophy. Therefore, the compositions of the present invention are indicated where an individual, particularly an elderly individual, has undergone surgery, or sustained an injury, or is afflicted With an illness that would dictate an extended period of inactivity, even in those situations like an injury to a limb, where only a portion of the body is immobilized.
Although the dosage regimen may be varied depending on the needs of the individual, the amount of the compositions of the present invention to be administered to a patient in need thereof in a single dosage is typically sufficient to provide from about 33 to 58 grams of the essential composition For most individuals in need of the essential compositions of the present invention, single dosages may be taken three times daily. While it is possible to take additional amounts on a daily basis, or take the total amount in a single daily dosage, three dosages over the course of a day, for example with meals, is recommended. Individual dosages in prepared form, whether in liquid or solid form, should contain from about 39 to 47 grams of the essential composition. Likewise, directions for use of a prepared powder to be added to food or, preferably, a liquid such as water or juice, should instruct the user to add a sufficient of the powder to provide the recommended dosage.
Throughout this application, there has been reference to an extended period of inactivity. How long it takes for muscles to begin to lose strength and subsequently begin to atrophy varies widely according to a number of factors including the age and general health and metabolism of the individual, the muscle strength and muscle tone of the individual, the surgical procedure, illness or injury requiring the forced inactivity and whether the individual must remain inactive, or only a portion of his or her body is immobilized, as where a cast is placed on a portion of the body or one or more appendages. Therefore, there is no way to definitely quantify the length of time for inactivity before the subject compositions would be recommended, except to note that they would be beneficial in any such circumstance due to their capacity to retard the process of loss of muscle strength. The following examples further illustrate the present invention, it being understood that they are in no way intended as limiting the scope thereof.
The following formulation is thoroughly mixed as a dry powder. Water is added gradually to the powder with stirring to form a suspension. Once the suspension is formed, sufficient additional water is added with stirring to bring the final volume to 12 ounces. The product is pasteurized and packaged. The 12 ounces of suspension is intended as a single dose and will provide 39.3 grams of the essential composition of the invention consisting of the first six listed ingredients, optionally including arginine.
The following ingredients are combined according to conventional techniques and formed into a nutrient bar. The bar, which is intended as a single dosage, contains 33 grams of the essential composition of the invention.
The following essential ingredients are blended together as a dry powder and the resultant formulator is blended with the excipient ingredients listed in Example 1, and is formulated into a 12 ounce suspension in the manner of Example 1. The essential composition of the formulation consists of the first six ingredients. Total weight of the essential composition is 58 grams
The following ingredients are combined according to conventional techniques and formed into a nutrient bar utilizing the excipient ingredients shown in Example 2. The bar, which is intended as a single dosage, will contain 41 grams of the essential composition of the invention.
