United States Patent 11» Howard et al. [54] COMPOSITIONS CONTAINING CREATINE [75] Inventors: Alan Norman Howard, Great Shelford; Roger Charles Harris, Newmarket, both of United Kingdom [73] Assigace: ‘The Howard Foundation, Cambridge, United Kingdom [21] Appl No: 08866817 (22) Flea: May 30,1997 [30] Foreign Application Posty Data May 31,1996 OH) led Kingdon oot1386 [51] Int. cL AGIK 9/14 [52] US. Ch 424/439; 424/489; 426/69 [58] Field of Search 424/489, 439; 13609 (50) References Cited US. PATENT DOCUMENTS 36150 10/971 Tombeck sona0 SSS ‘hose Dekel “033 mmol/l 60 e A t sol Nt t > 1 40 30 20 10 0 Boose Zam st 0 hours 05h USO05968544A_ uy) Patent Number: 5,968,544 [45] Date of Patent: Oct. 19, 1999 447453 31987 Meisner past Sons sis Neaner sien FOREIGN PATENT DOCUMENTS 0669083 8/1995 European Pat. Of 59.025663 2/1984 Japan 950087771 9/1996 Japan ‘9402127 2/1994 WIPO 96/15388 7/1994 WIPO 94/1704 8/1004 WIPO 96404240 2/1996 WIPO 96/14063 5/1996 WIPO 96/3648 11/1996 WIPO Primary Esaminer—Thurman K. Page Assistant Examiner—James M. Spear Attorney, Agent, or Firm—Lec, Mann, Smith, McWilliams, ‘Sweeney & Ohison (57) ABSTRACT Disclosed is an acidie composition for human consumption, comprising ereatine. In particular the composition is conve= nienlly an isotonic drink for storage at 4° C., or is a dry stable powder wich may be stored at ambient temperature 21 Claims, 6 Drawing Sheets . k se yP TUL ee Se eansgaUSS. Patent Oct. 19, 1999 Sheet 1 of 6 5,968,544 30 20 05h th 2h 3h 4h 6h 8 1 day 2d 3d 4d 1 week 2w 0 hours Fig. 1USS. Patent Oct. 19, 1999 Sheet 2 of 6 5,968,544 2/400m! 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 = s so yo so 2h 3h 4h 6h 8h 1d 2d 3d 4d Iw 2w Fig. 25,968,544 Sheet 3 of 6 Oct. 19, 1999 US. Patent % 100 90 80 70 60 50 40 30 20 10 MZ My PP pe PT PL U8 "9 Up We UZ UL uso 40 3 ig.USS. Patent Oct. 19, 1999 Sheet 4 of 6 5,968,544 105 100 95 90 % Cr 85 80 75 0.5h 4h 8h 1d 2d 3d Fig. 4USS. Patent Oct. 19, 1999 Sheet 5 of 6 5,968,544 102.0 100.0 2. > > % Creatine & & 94.0USS. Patent Oct. 19, 1999 Sheet 6 of 6 5,968,544 100 98 96 %Cr 94 92 90 Fig. 65,968,544 1 COMPOSITIONS CONTAINING CREATINE, FIELD OF THE INVENTION ‘This invention relates to compositions for human con- ‘sumption comprising creatine and to a method of providing ‘Stable ereatine-containing compositions. BACKGROUND OF THE INVENTION Governments are currently concerned with the high in dence of obesity (and lesser degrees of weight gain) in populations, since they represent a known risk-factor for ‘coronary heart disease, hypertension and diabetes. Besides ‘etary modification, the main thrust of treatment and weight ‘maintenance after weight loss is physical exercise. It is now ‘suggested by experts that det alone is insufficient in the long term in maintaining weight loss without altering lifestyle, in particular the taking of more exercise. However one of the problems overweight people experience is that they find physical activity tring and! are easily fatigued. There is a need for @ regime which will make obese people less fatigued! so that they can exercise for longer periods, burn up more calories and lose more weight, or maintain their weight better after weight loss. Moreover, inthe last few years there has been consider- able interest among athletes in creatine, which occurs abun- E al coneataton of creatine mozohydate (@1) Desc of preciiation tye bow pitas pats pile BOO . nae rrarry 72 a0 Relave preipaton: = bevy a — ‘The stability determination was performed as follows. 14 ‘gms of the formulation described in Example 4 were dis- solved in 250 ml of distilled water, Additionally 14 gms of second formulation were dissolved in 500 mls. The second {iormulation did not contain any creatine, but was otherwise identical to the formulation described in Example 4. 107 mls of the second solution were added to the first solution, producing a 7:3 dilution. Four 60 ml aliquots were removed and the plT adjusted with SM KOH to: A—unadjusted pH; B—pH 5.0, C—pH 6.0, D—pH 7.0 40 anl aliquots were removed for storage in plastic tubes at 4° C. 0.5 ml samples were removed from ACD and diluted disectly into 100 mi distilled water at 0 hhours, 2d, 7d, 14d, 28d, 35d and 52d for analysis of creatine and creatinine by HPLC, as described previously. The pH of the samples was also tested to ensure it had not varied over the course of the experiment, The results are shown below: TABLE 4 Hof sample over the cours of the experimen pit vues Ohh 24 7d__tad_—28s Sd A a8 aS a6 a6 a6 a6 36 Bosh sr S22 ost 2 Sh ©) 1 @l 61 el 1 ad Do) a a aH Tp CC) 20 40-40-80 DO Results of the analysis of the stability of creatine are shown below in Table 5. TABLES fedor fon}in mall. Dad __ ci semuibing on ny olf] 0 2 7 ek ows os ‘6079 OM 10 9A ORG 970 OD RT OR B SS40 O00 30) 200" 4 ORK 97D 960 9S © O32 noo io 1 98.7 9.7 993 986 ORG D S98 1M 34) 30390" 10 998 HH 98 ‘The above results are also represented graphically in FIG. 5. FIG. Sis a graph of % creatine remaining against time (in days). The open circles with solid line show the results for solution A, the solid circles with dotted line show the results for solution B, the open circles with dashed line show the results for solution C and the solid circles with dotted and dashed Tine show the results for solution D. These data demonstrate that even at a pH as low as 35-36, alter 5 weeks’ storage 4° C, only 7.3% of the creatine had been5,968,544 9 ine, and very litle further change had indicating that an equilibrium had been icant amounts of ereatin available for physiological benefit. Thus an acidic formulation compeis- dng cteatine can be prepared and stored successfully espe- cially with storage at temperatures lower than ambieat Example 7 ‘This examples relates to a study of the stability of creatine lover several Weeks in different (acidic) commercially avail- able yogurts, during storage at 4° C. The study was por formed as follows. (0.5 gms of ereatine monohydrate was mixed with 100 gms ‘of @ commercially available yogurt fo give a creatine eon- centration of about 3.4 mmol per 100 gms. The supple mented yogurt was placed in a domestic refrigerator set at 4° C. At various times, 2 ems ofthe supplemented youurt was taken up into 100 mis of distilled water. 1 ml ofthe resulting solution was filtered using a Whatman microfilter of pote size 12 kilodaltons, and the clear filtrate was assayed for creatine and creatinine concentrations as deseribed previ ously. Three diferent types of yogurt (purchased from ‘Tesco's stores) were uscd in the experiment, a low fat natural yogurt, a “healthy eating bio” youur, and a Fage Greek yogurt. The results ofthe reatine analysis are shown below ia Table 6, and ate cepresented graphically in FIG. 6 FIG. 6 shows a graph of &% creatine remaining against time {indays). The squares show the resuls forthe low fat youurt, the circles show the resut for the “bealthy eating” yosurt, and the triangles show the results for the Greek yogurt “The stability of creatine in the diferent yogurts was cextemely similae, The amouat of conversion of creatine t@ ‘reatinine was about 6% of less after 31 days’ storage at 4” C. The presence of live bacteria in the yogurt does. not appear 1 have any detrimental effect. ‘Thus yogurt represents an extremely useful vebicle for a ‘ereatine-comtaining composition, especially a8 Youuts ace ‘conventionally handled and stored at lower than ambieat temperatures—the presence of ereatine in the yogurt does not necessitate any additional handling. requirements in relation to temperature of storage. TABLE 6 Low st Heatty ‘atta eliag io yest yogi ‘Sang pl 3 42 7 va a 3 B 96? or 1% 961 963 38 982 oS 31 ou 3 We claim: 1. An acidic yogurt or similar semi-liquid foodstuif com- position for human consumption, said composition being lunflavored or fruit flavored, comprising creatine, said cre atine being substantially stable at ambient temperature or below. 2. A composition according to claim 1, comprising a fruit-lavoring, 0 as os ss ss 10 3. Acomposition according to claim 1, having a pH in the range 25-65 4. A composition according to claim 1, having a pH in the range 3.0-6.0. 5. A composition according to claim 1, comprising pyru- vate and/or dihydroxyacetone. 6. A.composition according to claim 1, comprising pyru- vate as the sodium, potassium, calcium or magnesium salts thereof, 7, Acomposition according to claim 1, comprising one ot more additional components selected from the group con- sisting of: vitamins, lipids, carbohydrates, amino acids, trace elements, colourings, flavors, artificial sweeteners, anti- oxidants, stabilisers, preservatives, and buffers. 8. A composition according to claim 1, provided as unitary doses. 9. Astable, dry powder composition comprising creatine, said composition being unflavored or fruit flavored, which, ‘when mixed with water or an aqueous solution, provides an acidic drink for human consumption, said creatine being substantially stable at ambient temperature or below. 10. A composition according to claim 9, wherein the ‘composition provides a drink which is isotonie and/or com- prises electrolytes. IL. A composition according to claim 9, wherein the ‘composition provides an isotonic drink comprising electro- lyes. 12. A composition according to claim 9, wherein the composition when dissolved in water provides a drink having a pH in the range 25-65. 13. A composition according to claim 12, providing a drink having a pH in the range 3.0-6.0, 14. A composition according 10 claim 9, comprising pyruvate andior dihydroxyacetone. 15. A composition according to claim 9, comprising pyruvate as the sodium, potassium, calcium or magnesium salts thereof, 16. A composition according to claim 9, comprising one ‘or more additional components selected from the group consisting of vitamins, lipids, carbohydrates, amino acids, trace elements, colourings, flavors, artificial sweeteners, anti-oxidants, stabilisers, preservatives, and buffers. 17. A composition according to claim 9, provided as unitary doses. 18. A composition according to claim 17, wherein each dose contains a physiologically effective quantity (of the order of 3 gms) of creatine. 19. A method of supplying an acidic ereatine-containing yogurt or similar semi-liquid foodstuff for human ‘consumption, the method comprising the steps of; obtaining 4 ereatine-containing substance; and mixing the creatine containing substances with a yogurt or similar semi-liquid foodstul. 20. A method of providing a creatine-containing acidic composition as a dry, stable powder which, when mixed with water or an aqueous solution gives an acidic fruit- flavored drink comprising creatine, the method comprising the steps of: providing a creatine-composition; drying the ‘composition; and packaging the dried composition, 21. A method according to claim 3, wherein the dried composition is packaged in unitary doses.