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AU2001253598B2 - A combination of pinitol and creatine to enhance uptake and retention of creatine - Google Patents

A combination of pinitol and creatine to enhance uptake and retention of creatine Download PDF

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Publication number
AU2001253598B2
AU2001253598B2 AU2001253598A AU2001253598A AU2001253598B2 AU 2001253598 B2 AU2001253598 B2 AU 2001253598B2 AU 2001253598 A AU2001253598 A AU 2001253598A AU 2001253598 A AU2001253598 A AU 2001253598A AU 2001253598 B2 AU2001253598 B2 AU 2001253598B2
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Prior art keywords
creatine
pinitol
composition
administration
active derivative
Prior art date
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Ceased
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AU2001253598A
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AU2001253598B9 (en
AU2001253598A1 (en
Inventor
John C. Dykstra
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ADVANTRX Corp
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ADVANTRX CORP
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Publication of AU2001253598B2 publication Critical patent/AU2001253598B2/en
Publication of AU2001253598B9 publication Critical patent/AU2001253598B9/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/02Nutrients, e.g. vitamins, minerals

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Nutrition Science (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

WO 01/80853 PCT/US01/12485 A COMBINATION OF PINITOL AND CREATINE TO ENHANCE UPTAKE AND RETENTION OF CREATINE FIELD OF THE INVENTION The invention relates to the use of pharmaceuticals and dietary supplements to enhance the uptake and retention of creatine in muscle, tissue.
BACKGROUND
Creatine phosphate is an excellent source of immediately available energy, capable of fueling the resynthesis of ATP from ADP.
Creatine is not synthesized in muscle tissue, but is transported to muscle tissue by the blood stream. Mankind has sought ways to accelerate ATP resynthesis and improve muscle power and performance by enhancing creatine uptake and retention by the muscle tissue. Such efforts range from the consumption of mass quantities of creatine to the administration of a combination of creatine and any of a variety of adjuvants, such as insulin and/or a carbohydrate.
While certain of these techniques have demonstrated limited success in enhancing creatine uptake and/or retention in muscle tissues, the search continues for safe alternative means for improving muscle performance by enhancing creatine uptake and retention in muscle tissue.
WO 01/80853 PCT/US01/12485 SUMMARY OF THE INVENTION We have discovered that muscle performance can be improved and muscle hypertrophy enhanced, through enhanced uptake and retention of creatine resulting in improved ATP resynthesis, by administering an effective synergistic amount of a combination of creatine or an active derivative thereof and pinitol or an active derivative or metabolite thereof.
DETAILED DESCRIPTION OF THE INVENTION INCLUDING A BEST MODE The First Active Ingredient The first active ingredient is creatine or an active derivative thereof.
Creatine has the structure shown below in Figure 1.
CH
20oN NH r COOH H2 Creatine is commercially isolated from meat extracts and is available from a number of sources. Creatine is generally available and suitable for use in the invention as a monohydrate, with the monohydrate converted to anhydrous form at about 100 0
C.
Suitable derivatives of creatine include creatine phosphates, creatine citrate, creatine ascorbate, creatine pyruvate, cyclo-creatine and other salts thereof.
WO 01/80853 PCT/US01/12485 The Second Active Ingredient The second active ingredient is pinitol or an active derivative or metabolite thereof. Pinitol has the structure shown below in Figure 2.
OH
OH
OH OH Pinitol can be extracted from a number of plant sources, including alfalfa, Bougainvillea leaves, chick peas, pine trees and soy beans, and is commercially available from Humanetics Corporation under the trademark InzitolM.
Suitable derivatives and metabolites of pinitol include pinitol glycosides, pinitol phospholipids, esterified pinitol, lipid-bound pinitol, pinitol phosphates, pinitol phytates, and hydrolyzed pinitol such as d-chiro-inositol.
Optional ThirdActive Ingredient The composition can optionally include a third active ingredient of a carbohydrate or an active derivative thereof an organic aldehyde or ketone compound having multiple hydroxyl groups). The carbohydrate is preferably a simple carbohydrate, such as fructose or glucose.
Administration ADMINISTRATION ROUTE The active ingredients can be administered to any mammal, including humans, for whom an improvement in muscle performance and/or enhanced muscle hypertrophy is desired.
WO 01/80853 PCT/US01/12485 The active ingredients can be administered individually or together by virtually any of the commonly accepted practices for the administration of pharmaceutical preparations and dietary supplements including specifically, but not exclusively, mucosal administration, oral consumption, ocular administration, subcutaneous injection, transdennal administration, etc. In order to achieve the desired synergistic effect, the creatine and pinitol should be administered so that the blood plasma level of pinitol is elevated simultaneously with or prior to administration of creatine. In a preferred embodiment, the creatine and pinitol are blended together in a single composition and administered together.
Mucosal administration of the active ingredients includes such routes as buccal, endotracheal, nasal, pharyngeal, rectal, sublingual, vaginal, etc. For administration through the buccal/sublingual/pharyngealendotracheal mucosa, the ingredients may be formulated as an emulsion, gum, lozenge, spray, tablet or an inclusion complex such as cyclodextrin inclusion complexes. Nasal administration is conveniently conducted through the use of a sniffing power or nasal spray. For rectal and vaginal administration, the ingredients may be formulated as a cream, douche, enema or suppository.
Oral consumption of the active ingredients may be effected by incorporating the ingredients into a food or drink, formulating the ingredients into a chewable or swallowable tablet, or formulating the ingredients as a powdered or granular dietary supplement.
Ocular administration may be effected by incorporating the active ingredients into a solution or suspension adapted for ocular application such as drops or sprays.
Subcutaneous administration involves incorporating the active ingredients into a pharmaceutically acceptable and injectable carrier.
WO 01/80853 PCT/US01/12485 For transdermal administration, the active ingredients may be conveniently incorporated into a lipophilic carrier and formulated as a topical creme or adhesive patch.
DOSE RATE The range of dosages and dose rates effective for achieving the desired synergistic improvement in muscle performance and enhanced muscle hypertrophy may be determined in accordance with standard industry practices. As a general guide, a dose rate of about 5 to 20 grams of creatine per day, accompanied by appropriate amounts of pinitol and any carbohydrate, should provide the desired biological response of improved muscle performance and enhanced muscle hypertrophy.
Administration can be effected on any desired schedule with a preference for administration with every meal, daily or a few hours prior to each workout or other athletic activity.
RATIO OF FIRST INGREDIENT TO SECOND INGREDIENT The range of relative percentages of creatine and pinitol the active ingredients) effective for achieving the desired synergistic improvement in muscle performance and enhanced muscle hypertrophy may similarly be determined in accordance with standard industry practices. As a general guide, a weight ratio of pinitol or active derivative or metabolite thereof to creatine or active derivative thereof between 1:10,000 to 1:1 should provide the desired biological response of improved muscle performance and enhanced muscle hypertrophy. Preferred ratios are between about 1:200 100 mg of pinitol to 20 grams of creatine) to about 1:2 1 g of pinitol to 2 grams of creatine).

Claims (51)

1. A composition, comprising: pinitol or an active derivative or metabolite thereof and creatine or an active derivative thereof.
2. The composition of claim 1 wherein the creatine is creatine monohydrate.
3. The composition of claim 1 wherein the weight ratio of pinitol or active derivative or metabolite thereof to creatine or active derivative thereof is between 1:10,000 to 1:1.
4. The composition of claim 1 wherein the composition is in powder or granular form. The composition of claim 1 wherein the composition is in tablet form.
6. The composition of claim 1 wherein the composition further includes a carbohydrate or an active derivative thereof.
7. A method of increasing creatine retention in a mammal comprising substantially simultaneously increasing the blood plasma level of creatine and pinitol.
8. The method of claim 7 wherein the mammal is a human.
9. The method of claim 7 wherein the blood plasma level of creatine is increased by the administration of creatine.
10. The method of claim 9 wherein the administration of creatine comprises oral consumption of creatine.
11. The method of claim 10 wherein the creatine is creatine monohydrate. 6 WO 01/80853 PCT/US01/12485
12. The method of claim 7 wherein the blood plasma level of pinitol is increased by the administration of pinitol.
13. The method of claim 12 wherein the administration of pinitol comprises oral consumption of pinitol.
14. The method of claim 10 wherein the blood plasma level of pinitol is increased by the oral consumption of pinitol. The method of claim 14 wherein the weight ratio of pinitol to creatine is between 1:10,000 to 1:1.
16. The method of claim 14 wherein the composition is in powder or granular form.
17. The method of claim 14 wherein the composition is in tablet form.
18. The method of claim 14 wherein the composition is consumed daily.
19. The method of claim 14 wherein at least 5 grams of creatine and at least 2 mg ofpinitol are consumed daily. The method of claim 19 wherein at least 5 grams of creatine and at least 10 mg ofpinitol are consumed daily.
21. A method of increasing cell up-take of creatine in a mammal comprising the substantially simultaneous administration of creatine or active derivative thereof and pinitol or active derivative or metabolite thereof.
22. The method of claim 21 wherein the mammal is a human. WO 01/80853 PCT/US01/12485
23. The method of claim 22 wherein the administration of creatine comprises oral consumption of creatine.
24. The method of claim 23 wherein the creatine is creatine monohydrate. The method of claim 22 wherein the administration of pinitol comprises oral consumption ofpinitol.
26. The method of claim 25 wherein the administration of creatine comprises oral consumption of creatine.
27. The method of claim 26 wherein the weight ratio ofpinitol to creatine is between 1:10,000 to 1:1.
28. The method of claim 27 wherein the composition is in powder or granular form.
29. The method of claim 27 wherein the composition is in tablet form.
30. The method of claim 27 wherein the composition is consumed daily.
31. The method of claim 27 wherein at least 2 mg of pinitol and at least 5 grams of creatine are consumed daily.
32. The method of claim 31 wherein at least 10 mg of pinitol and at least 5 grams of creatine are consumed daily.
33. The method of claim 22 wherein the method of increasing cell up-take of creatine comprises increasing muscle cell up-take of creatine.
34. A method of accelerating ATP resynthesis in a mammal comprising the substantially simultaneous administration of creatine or active derivative thereof and pinitol or active derivative or metabolite thereof. 8 WO 01/80853 PCT/US01/12485 The method of claim 34 wherein the mammal is a human.
36. The method of claim 35 wherein the administration of creatine comprises oral consumption of creatine.
37. The method of claim 36 wherein the creatine is creatine monohydrate.
38. The method of claim 35 wherein the administration of pinitol comprises oral consumption of pinitol.
39. The method of claim 38 wherein the administration of creatine comprises oral consumption of creatine.
40. The method of claim 39 wherein the weight ratio of pinitol to creatine is between 1:10,000 to 1:1.
41. The method of claim 40 wherein the composition is in powder or granular form.
42. The method of claim 40 wherein the composition is in tablet form.
43. The method of claim 40 wherein the composition is consumed daily.
44. The method of claim 40 wherein at least 2 mg of pinitol and at least 5 grams of creatine are consumed daily. The method of claim 44 wherein at least 10 mg of pinitol and at least 5 grams of creatine are consumed daily.
46. The method of claim 22 wherein the method of accelerating the rate of ATP resynthesis comprises accelerating the rate of ATP resynthesis in muscle cells. WO 01/80853 PCT/US01/12485
47. A method of increasing muscle hypertrophy in a mammal comprising the substantially simultaneous administration of creatine or active derivative thereof and pinitol or active derivative or metabolite thereof.
48. The method of claim 47 wherein the mammal is a human.
49. The method of claim 48 wherein the administration of creatine comprises oral consumption of creatine.
50. The method of claim 49 wherein the creatine is creatine monohydrate.
51. The method of claim 48 wherein the administration of pinitol comprises oral consumption of pinitol.
52. The method of claim 51 wherein the administration of creatine comprises oral consumption of creatine.
53. The method of claim 52 wherein the weight ratio of pinitol to creatine is between 1:10,000 to 1:1.
54. The method of claim 53 wherein the composition is in powder or granular form. The method of claim 53 wherein the composition is in tablet form.
56. The method of claim 53 wherein the composition is consumed daily.
57. The method of claim 53 wherein at least 2 mg of pinitol and at least 5 grams of creatine are consumed daily.
58. The method of claim 57 wherein at least 10 mg of pinitol and at least 5 grams of creatine are consumed daily.
AU2001253598A 2000-04-19 2001-04-16 A combination of pinitol and creatine to enhance uptake and retention of creatine Ceased AU2001253598B9 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US19839000P 2000-04-19 2000-04-19
US60/198,390 2000-04-19
PCT/US2001/012485 WO2001080853A1 (en) 2000-04-19 2001-04-16 A combination of pinitol and creatine to enhance uptake and retention of creatine

Publications (3)

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AU2001253598A1 AU2001253598A1 (en) 2002-01-24
AU2001253598B2 true AU2001253598B2 (en) 2005-12-15
AU2001253598B9 AU2001253598B9 (en) 2006-02-23

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AU5359801A Pending AU5359801A (en) 2000-04-19 2001-04-16 A combination of pinitol and creatine to enhance uptake and retention of creatine
AU2001253598A Ceased AU2001253598B9 (en) 2000-04-19 2001-04-16 A combination of pinitol and creatine to enhance uptake and retention of creatine

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AU (2) AU5359801A (en)
CA (1) CA2405992A1 (en)
GB (1) GB2377639B (en)
NZ (1) NZ522317A (en)
WO (1) WO2001080853A1 (en)

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DE3221827A1 (en) * 1982-06-09 1983-12-15 DSO Pharmachim, Sofija BIOSTIMULATING AGENT
US5834473A (en) * 1993-04-29 1998-11-10 Cultor, Ltd. Method for treating coccidiosis
JP2003511094A (en) * 1999-10-18 2003-03-25 マッスルテク リサーチ アンド ディヴェロプメント インコーポレーション Dietary supplements to increase lean body mass and physical fitness

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GB2377639A8 (en) 2003-11-27
GB0225557D0 (en) 2002-12-11
AU5359801A (en) 2001-11-07
CA2405992A1 (en) 2001-11-01
AU2001253598B9 (en) 2006-02-23
WO2001080853A1 (en) 2001-11-01
NZ522317A (en) 2004-05-28
GB2377639B (en) 2004-10-13
GB2377639A (en) 2003-01-22

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Owner name: ADVANTRX CORPORATION

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