Patent Publication Number: US-2009221502-A1

Title: Vegetarian anabolic protein composition

Description:
CLAIM OF PRIORITY OF PROVISIONAL APPLICATION 
     The present application claims the priority of U.S. provisional application 61/009,107 filed on Dec. 24, 2007. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The invention relates to nutritional supplements and specifically to an orally ingested completely vegetarian protein supplement that closely matches the amino acid composition of human muscle and improves physical performance and overall health and is also useful for treating or ameliorating certain human diseases and conditions. 
     2. Brief Description of the Prior Art 
     High-intensity weight (resistance) training causes muscle anabolism by multiple mechanisms. (Godfrey R J. et al.  Sports Medicine  2003; 33(8): 599-613; Falk et al.  Pediatr Endocrinol Rev  2003; 1(2): 120-7). Although the inventors do not wish to be bound by theory, a prominent theoretical basis for rate-limitation in muscle anabolism is the “depletion theory.” According to this theory, the extent and rate of muscle anabolism is limited by whichever micro- or macro-nutrient is first depleted as “building blocks” in the nutrient supply to the growing muscle tissue. Hence weight trainers and other athletes who seek muscle hypertrophy commonly take protein dietary supplements. The common protein dietary supplements recommended and consumed to attain muscle anabolism include concentrated or isolated whey or soy proteins as their main component. The whey and soy proteins are usually obtained as byproducts of cheese or of soybean oil manufacture, respectively, and they are indeed reasonably good quality dietary proteins that show good benefit in human nutrition. (Yalcin.  Curr Phar. Des.  2006; 12(13): 1637-43; Ha et al.  J Nutr Biochem.  2003; 14(5):251-8; Haub et al.  Am J Clin Nutr.  2002; 76(3): 511-7; Jeejeebhoy.  Eur J Gastroenterol Hepatol.  2000; 12(1): 1-2. 
     However, for the specific purpose of muscle anabolism, it would be desirable and would attain better results to have a dietary supplement of a composition that, as far as amino acids are concerned, most closely matches the composition of human muscle. As Table 1 below shows whey and soy proteins do not closely match the amino acid composition of human muscle because they are deficient in several amino acids that are present in human muscle tissue. In accordance with the depletion theory of anabolism and practical considerations also, the lack or mismatch in percentage of certain amino acids between the respective protein supplement and human muscle is likely to limit the rate at which human muscle anabolism could be obtained. 
                     TABLE 1                  Human muscle composition (Matthews. Modern Nutrition in       Health and Disease. Baltimore, Md: Williams &amp; Wilkins; 2006:       23-58) along with soy (Karr-Lilienthal et al. J. Agric Food Chem.       2004; 52(20): 6193-9) and whey protein isolates (McDonough       et al. J Dairy Sci 1974; 57(12): 1438-43)                                     Human Muscle   Percentage   Soy   Whey Protein       3-Letter Amino   Composition   in human   Protein   Isolate       Acid Code   (mg/g)   muscle   (mg/g)   (mg/g)                                         ILE   31.5   5.18   43   51       LEU   53.3   8.76   71   113       LYS   56.6   9.3   55   104       MET   16.9   2.78   11   21       PHE   29.9   4.91   45   33       THR   31   5.1   33   42       TRP   7.5   1.23   12   25       VAL   36.7   6.03   44   48       CYS   9.7   1.59   11   15       HIS   18.6   3.06   23   20       TYR   20.5   3.37   33   34       ALA   43.5   7.15   37   45       ARG   44.2   7.26   66   22       GLX   54.8   9.01   166   156       GLY   33.6   5.52   37   15       PRO   30.2   4.96   44   41       SER   36.9   6.07   0   26       ASX   53   8.71   101   105       Total mg/g   608.4   99.99   832   916                    
An additional problem in the current art is that the number of vegetarian and vegan consumers is increasing while most high quality protein sources are derived from animal ingredients, specifically whey proteins, milk proteins, and egg proteins. Vegetarian protein sources are highly deficient in multiple amino acids (see soy in Table 1). Moreover, dependence on a single source of protein supply, such as whey or soy protein isolate or concentrate, is considered undesirable in the art for multiple reasons, including commercial ones.
 
     There is therefore an unmet need in the art to supply a dietary protein supplement that closely matches the amino acid composition of human muscle tissue, is not deficient in any amino acids, is completely vegetarian and does not depend on a single protein source. The dietary supplement composition of the present invention meets this need. 
     SUMMARY OF THE INVENTION 
     Vegetarian amino acid sources are combined to create a protein blend that closely matches human muscle tissue in terms of amino acid composition. In the context of this application “closely matching” means that the amino acid composition of the protein blend is within five percent (5%) of the amino acid composition of human muscle for all of the amino acids, as shown in Table 1. The protein blend can be used as food or food supplement to facilitate and bolster muscle anabolism for healthy humans desiring such result and also to treat and or ameliorate the effects of certain diseases and conditions such as sarcopenia, cancer cachexia, HIV wasting, malnutrition, primary muscle diseases (myopathy) and side effects of corticosteroid therapy. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Soy protein isolate, pea protein concentrate, rice protein isolate, l-lysine, l-glycine and l-alanine are mixed to match the human muscle composition. The amino acid composition of the blends is compared to the amino acid composition of human muscle. A “match” of each combination of the five (5) ingredients is assessed by computing the total sum of squares of differences between the amino acid compositions of the blend with that of human muscle. 
     Best fit to human muscle is established by minimizing the total sum of squares of differences between the blend and human muscle by varying the five (5) ingredients using any automated algorithm. Any algorithm that utilizes the method of least squares (see for example Å. Björck,  Numerical Methods for Least Squares Problems,  Cambridge, 1996) can be used; a suitable one is the SOLVER plug-in (Frontline Systems, Inc., Incline Village, Nev.) to Microsoft Excel (Microsoft Corporation, Redmond, Wash.). An additional constraint is added that the resultant blend may not be lacking any amino acid of the human muscle and must be a “close match” as defined above. Preferably no amino acid is present in the blend in lesser percentage than in the human muscle as shown in Table 1. 
     In accordance with the following considerations a dietary composition is provided in accordance with the present invention that, in addition to usual and/or optional excipients, contains the following combination of ingredients: 
     Two or more vegetable proteins selected from the group consisting of soy protein, rice protein, pea protein, buckwheat protein, wheat protein, potato protein, sunflower protein, safflower protein, hops protein and mustard protein, and one or more of the isolated amino acids selected from the group consisting of lysine, glycine and alanine, with the further condition that the amino acid composition of the blend closely matches the amino acid composition of the human muscle, as disclosed in Table 1. Acceptable percentages of ingredients the appropriate combination of which can provide the blend satisfying the above stated criteria are, for example
     1.0-8.5% soy protein isolate   10.5-19% pea protein isolate   72-76% rice protein isolate   1.5-3.5% lysine and   0.5-1.5% glycine   and   1-20% buckwheat   24-32% pea   46-62% rice   1.5-3.5% lysine   0.5-1.5% glycine   1.5-2.5% alanine   

     Applicants understand that the total percentage of the active ingredients or components shown above (and not even considering optional excipients) cannot exceed 100%. Therefore, the actual percentages of the active ingredients are to be selected such that their total is 100%, and this 100% of the active components is then diluted with optional excipients well known in the art. 
     The dietary composition or blend of the present invention may be in the form of tablets, capsules, two-piece hard gelatin capsules, effervescent tablets, powdered drink mix, drink blend and protein bar. The foregoing indicated percentages refer only to the listed ingredients and do not include the weight of the other excipeints that are usually present in the composition or formulation.
 
Tablets are the presently one preferred composition of the blend of the invention. A broad example of the composition of the tablet or other unitary dose of the composition is shown below.
 
                                                 Amount           Ingredient   Per Tablet                          Soy Protein Isolate   10-900           Pea Protein Isolate   10-900           Rice Protein Isolate   10-900           L-Lysine HCl Gran (80% Lysine)    1-100           Glycine USP (Aminoacetic Acid)    1-100                        
The numbers refer to milligrams (mg) of ingredient per single tablet, capsule or other unitary dose of the formulation. In addition to the listed ingredients usual pharmaceutically acceptable excipients may also be present in the tablet or other unitary dose.
 
     More preferably, in addition to usual and/or optional excipients, the formulation contains the following combination of ingredients in the amounts indicated. Again, the numbers refer to milligrams of ingredient per single tablet, capsule or other unitary dose of the formulation. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                   
                 Amount 
               
               
                   
                 Ingredient 
                 Per Tablet 
               
               
                   
                   
               
             
            
               
                   
                 Soy Protein Isolate 
                 20-500 
               
               
                   
                 Pea Protein Isolate 
                 20-500 
               
               
                   
                 Rice Protein Isolate 
                 400-900  
               
               
                   
                 L-Lysine HCl Gran (80% Lysine) 
                 5-75 
               
               
                   
                 Glycine USP (Aminoacetic Acid) 
                 5-75 
               
               
                   
                   
               
            
           
         
       
     
     Even more preferably, in addition to usual and/or optional excipients, the formulation contains the following combination of ingredients in the amounts indicated. (The numbers refer to milligrams of ingredient per single tablet, capsule or other unitary dose of the formulation.) 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                   
                 Amount 
               
               
                   
                 Ingredient 
                 Per Tablet 
               
               
                   
                   
               
             
            
               
                   
                 Soy Protein Isolate 
                 50-100 
               
               
                   
                 Pea Protein Isolate 
                 50-150 
               
               
                   
                 Rice Protein Isolate 
                 600-900  
               
               
                   
                 L-Lysine HCl Gran (80% Lysine) 
                 10-50  
               
               
                   
                 Glycine USP (Aminoacetic Acid) 
                 5-20 
               
               
                   
                   
               
            
           
         
       
     
     In terms of percentages of the essential ingredients (not considering the weight of excipients), examples of the formulation are 
     (1) a Protein Composition Essentially Consisting of 
     
         
         8% soy protein isolate 
         11% pea protein isolate 
         74% rice protein isolate 
         3% l-lysine 
         1% glycine, 
         and 
       
    
     (2) a Protein Composition Essentially Consisting of 
     
         
         19% buckwheat protein concentrate (available from Cyvex Nutrition, Irvine, Calif.), 
         28% pea protein isolate 46%, 
         rice protein isolate 2%, 
         l-lysine 1%, 
         glycine 2%, 
         beta-alanine (available from Natural Alternatives International, San Marcos, Calif.).
 
The weights in milligrams or percentages in the exemplary formulations above are selected in such a way that the criteria of closely matching the amino acid composition of the human muscle are met.
 
Another preferred exemplary formulation of the anabolic protein composition of the invention is in the form of a powder that can be sweetened and flavored to be mixed with water and taken as a beverage. A unitary dose, recommended as a single daily dose, of this exemplary formulation has the following ingredients in the following ranges.
 
         Soy protein isolate 0.1 to 30 grams; 
         Pea protein isolate 0.1 to 30 grams; 
         Rice protein isolate 0.1 to 30 grams; 
         L-Lysine HCl Gran (80% Lysine) 0.1 to 3 grams; 
         Glycine USP (aminoacetic acid) 0.1 to 3 grams; 
         Maltodextrin (optional) 1 to 10 grams; 
         Sucralose (optional sweetener, or other sweetener) 0.05 to 0.5 grams; 
         Acesulfame potassioum (optional) 0.001 to 0.02 grams, and 
         Natural and/or artificial vanilla flavor (optional., or other flavor) 0.1 to 1 gram.
 
This unitary dose is designed to be mixed with approximately 8 ounces of cold water and consumed as a beverage.
 
       
    
     Presently Preferred Actual Formulation, Specific  Embodiment  
     The presently preferred specific embodiment has the following five (5) essential ingredients of the inventive composition as shown below. (The numbers refer to milligrams per tablet, or other formulation such as a capsule or the like.) 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                   
                 Amount 
               
               
                   
                 Ingredient 
                 Per Tablet 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 Soy Protein Isolate 
                 80 
               
               
                   
                 Pea Protein Isolate 
                 110 
               
               
                   
                 Rice Protein Isolate 
                 740 
               
               
                   
                 L-Lysine HCl Gran (80% Lysine) 
                 37.5 
               
               
                   
                 Glycine USP (Aminoacetic Acid) 
                 10.15 
               
               
                   
                   
               
            
           
         
       
     
     Table 2 below shows in a different manner the best-fit combination of the five (5) essential ingredients, soy protein isolate, pea protein concentrate, rice protein isolate, l-lysine and l-glycine that is all vegetarian and best approximates in terms of amino acid composition the composition of human muscle. This best fit combination is the presently most preferred and specific embodiment of the present invention. As is indicated in the table weights, ratios or proportions are indicated as milligram per gram (mg/g). Table 2 also provides comparison with whey protein isolate that is not used in accordance with the present invention. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Amino Acid composition of the preferred embodiment 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 I 
                   
                 K 
               
               
                   
                   
                 B 
                   
                   
                   
                   
                   
                   
                 Square of 
                 J 
                 Square of 
               
               
                   
                 A 
                 Human 
                 C 
                 D 
                 E 
                   
                   
                 H 
                 Difference 
                 Whey 
                 Difference 
               
               
                   
                 3-Letter 
                 Muscle 
                 Soy 
                 Pea 
                 Rice 
                 F 
                 G 
                 Invented 
                 (invention − 
                 Protein 
                 (whey − 
               
               
                   
                 Amino 
                 Comp 
                 Protein 
                 Protein 
                 Protein 
                 Lysine 
                 Glycine 
                 composition 
                 human 
                 Isolate 
                 human 
               
               
                 1 
                 Acid Code 
                 (mg/g) 
                 (mg/g) 
                 (mg/g) 
                 (mg/g) 
                 (mg) 
                 (mg) 
                 (mg/g) 
                 muscle) 
                 (mg/g) 
                 muscle) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 2 
                 ILE 
                 31.5 
                 43 
                 43.9 
                 39.6 
                   
                   
                 37.6 
                 37 
                 51 
                 380 
               
               
                 3 
                 LEU 
                 53.3 
                 71 
                 85.1 
                 74.8 
                   
                   
                 70.4 
                 292 
                 113 
                 3564 
               
               
                 4 
                 LYS 
                 56.6 
                 55 
                 76.9 
                 30.6 
                 800 
                   
                 59.5 
                 8 
                 104 
                 2247 
               
               
                 5 
                 MET 
                 16.9 
                 11 
                 7.2 
                 28.5 
                   
                   
                 22.8 
                 34 
                 21 
                 17 
               
               
                 6 
                 PHE 
                 29.9 
                 45 
                 57.6 
                 49 
                   
                   
                 46.2 
                 266 
                 33 
                 10 
               
               
                 7 
                 THR 
                 31 
                 33 
                 120 
                 33.12 
                   
                   
                 40.3 
                 87 
                 42 
                 121 
               
               
                 8 
                 TRP 
                 7.5 
                 12 
                 7.9 
                 10.8 
                   
                   
                 9.8 
                 5 
                 25 
                 306 
               
               
                 9 
                 VAL 
                 36.7 
                 44 
                 49.3 
                 54 
                   
                   
                 48.9 
                 149 
                 48 
                 128 
               
               
                 10 
                 CYS 
                 9.7 
                 11 
                 8.3 
                 22 
                   
                   
                 18.1 
                 70 
                 15 
                 28 
               
               
                 11 
                 HIS 
                 18.6 
                 23 
                 24.5 
                 19 
                   
                   
                 18.6 
                 0 
                 20 
                 2 
               
               
                 12 
                 TYR 
                 20.5 
                 33 
                 39.6 
                 48.6 
                   
                   
                 43 
                 504 
                 34 
                 182 
               
               
                 13 
                 ALA 
                 43.5 
                 37 
                 40 
                 48.9 
                   
                   
                 43.5 
                 0 
                 45 
                 2 
               
               
                 14 
                 ARG 
                 44.2 
                 66 
                 8.2 
                 82.3 
                   
                   
                 67.1 
                 524 
                 22 
                 493 
               
               
                 15 
                 GLX 
                 54.8 
                 166 
                 184.5 
                 154.9 
                   
                   
                 148.2 
                 8724 
                 156 
                 10241 
               
               
                 16 
                 GLY 
                 33.6 
                 37 
                   
                 38.2 
                   
                 985 
                 41.1 
                 56 
                 15 
                 346 
               
               
                 17 
                 PRO 
                 30.2 
                 44 
                 40.8 
                 44.8 
                   
                   
                 41.2 
                 120 
                 41 
                 117 
               
               
                 18 
                 SER 
                 36.9 
                   
                 53.2 
                 43.2 
                   
                   
                 37.8 
                 1 
                 26 
                 119 
               
               
                 19 
                 ASX 
                 53 
                 101 
                 120 
                 77.5 
                   
                   
                 78.6 
                 657 
                 105 
                 2704 
               
               
                 20 
                 Total mg/g 
                 608.4 
                 832 
                 967 
                 899.82 
                   
                   
                 838.8 
                   
                 916 
               
               
                 21 
                 Cost/kg 
                   
                 $5.70 
                 $6.50 
                 $6.75 
                 $6.83 
                 $6.32 
                 $6.43 
                   
                 $9.35 
               
               
                 22 
                 Fraction 
                   
                 0.08 
                 0.11 
                 0.74 
                 0.03 
                 0.01 
                   
                   
                   
                   
               
               
                 23 
                 Sum of 
                   
                   
                   
                   
                   
                   
                   
                 11534.9 
                   
                 21007 
               
               
                   
                 Square of 
               
               
                   
                 Differences 
               
               
                   
               
            
           
         
       
     
     By way of explanation of Table 2, Column B shows the amino acid composition of human muscle tissue as milligrams of amino acid per gram of human muscle tissue. (Matthews.  Modern Nutrition in Health and Disease.  Baltimore, Md.: Williams &amp; Wilkins; 2006:23-58). 
     Columns C, D, and E show the typical amino acid composition of soy protein isolate obtained from a typical commercial source (for example from the Archer Daniels Midland Corporation, Decatur, Ill.), of pea protein isolate obtained from a typical commercial source (Parrheim Foods, Saskatoon, SK, Canada), and rice protein isolate obtained from a typical commercial source (Oryzatein™, Axiom Foods, Santa Monica, Calif.) as milligrams of amino acid per gram of total product. 
     Columns F and G show the “amino acid composition” of the pure amino acid materials l-lysine obtained from a typical commercial source (Ajinomoto Amino Science LLC, Raleigh, N.C.) and of glycine obtained from a typical commercial source (Ajinomoto Amino Science LLC, Raleigh, N.C.). 
     Column H shows the amino acid composition of the combination of soy protein, pea protein, rice protein, lysine and glycine in the ratios prescribed by row 22 (see below). This is the amino acid composition of the preferred embodiment of the presently invention. 
     Column I shows the Square of the Differences between the “Invention” amino acid composition (column H) and the amino acid composition of human muscle tissue (column B). These numbers are added together to give the total sum of the square of the differences, which is reported in row 23. 
     Column J shows the amino acid composition of whey protein isolate obtained from a typical commercial source (Davisco Foods International, Inc. Le Sueur, Minn.) by comparison. 
     Column K shows the Square of the Differences between whey protein amino acid composition (column J) and the amino acid composition of human muscle tissue (column B). These numbers are added together to give the total sum of the square of the differences, which is reported in row 23. 
     Row 21 shows the current commercial cost per kilo for the various protein and amino acid sources. 
     Row 22 shows the relative fraction of the five ingredients (soy protein, pea protein, rice protein, lysine, and glycine) combined to make the presently preferred specific embodiment of the invention. The relative fractions sum to nearly one (1) disclosing the proportions of all essential ingredients of the composition. 
     The vegetarian blend shown in Table 2 exhibits a fit to human muscle protein better than any of the pure protein sources (soy, whey, rice, pea) and is superior to any other combination of ingredients. It additionally is less expensive than whey protein and can be considered 100% “vegetarian.” 
     This blend was combined along with other vegetarian excipient ingredients such as microcrystalline cellulose, calcium phosphate dibasic, croscarmellose sodium, stearic acid, silicon dioxide, magnesium stearate and a hydroxypropylmethylcellulose/triacetin coating into a formulation shown in Table 3. Although a tablet formulation is the presently preferred specific embodiment of the invention, those skilled in the art will readily understand that the protein and amino acid components of the invention can be combined in the ratios indicated above with additional and/or other excipients to provide other tablet and other well known formulations, such as without limitation capsules, powders for drinks, protein bars, that are within the scope of the invention. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Tablet formulation of one specific embodiment 
               
            
           
           
               
               
               
            
               
                   
                   
                 Amount 
               
               
                   
                 Ingredient 
                 Per Tablet 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 Soy Protein Isolate 
                 80 
               
               
                   
                 Pea Protein Isolate 
                 110 
               
               
                   
                 Rice Protein Isolate 
                 740 
               
               
                   
                 L-Lysine HCl Gran (80% Lysine) 
                 37.5 
               
               
                   
                 Glycine USP (Aminoacetic Acid) 
                 10.152 
               
               
                   
                 Microcrystalline Cellulose 
                 200 
               
               
                   
                 Calcium Phosphate Dibasic 
                 200 
               
               
                   
                 Croscarmellose Sodium 
                 50 
               
               
                   
                 Stearic acid 
                 60 
               
               
                   
                 Silicon dioxide 
                 20 
               
               
                   
                 Magnesium Stearate 
                 20 
               
               
                   
                 Aqueous film coating consisting 
                 15 
               
               
                   
                 Of hydroxypropylmethylcellulose 
               
               
                   
                 And triacetin (Opadry YS-2-7035) 
               
               
                   
                   
               
            
           
         
       
     
     The formulation shown in Table 3 was blended using a cross-flow powder mixer, compressed into tablets using a rotary tablet press of standard design and coated using an aqueous film coater of standard design. 
     A specific embodiment of the formulation that is to be used as a powder mixed with water and consumed as a beverage is as follows.
     Soy protein isolate 2.4 grams;   Pea protein isolate 3.3 grams;   Rice protein isolate 22.2 grams;   L-Lysine HCl Gran (80% Lysine) 1.1 grams;   Glycine USP (aminoacetic acid) 0.3 grams;   Maltodextrin 2.9 grams;   Sucralose 0.19 grams;   Acesulfame potassioum 0.006 grams, and   Natural &amp; artificial vanilla flavor 0.48 grams.
 
This unitary dose is to be mixed with approximately 8 ounces of cold water.
   

     The vegetarian tablets or LIKE formulations in accordance with the invention are to be swallowed by humans to induce or increase muscle anabolism in healthy humans who desire such result and for treating and or ameliorating the effects of certain diseases and conditions such as sarcopenia, cancer cachexia, HIV wasting, malnutrition, primary muscle diseases (myopathy) and side effects of corticosteroid therapy. 
     The recommended dosage is 1 to 20 tablets (or equivalent unitary dose formulations) per day, more preferably 5 to 15 tablets (or equivalent unitary dose formulations) per day, and most preferably nine (9) tablets (or equivalent unitary dose formulations) per day. In case of the formulation to be used as a powder to be mixed with water and consumed as a beverage the recommended dose is one unitary dose, as defined above, per day.