Compositions comprising methylxanthine and enzymatically converted disaccharides derived from sucrose

Abstract

Compositions comprising methylxanthine in combination with an enzymatically converted disaccharide derived from sucrose are disclosed. More particularly, the present invention discloses compositions comprising methylxanthine and an enzymatically converted disaccharide derived from sucrose, the disaccharide selected from the group consisting of pinose, leuconostoc disaccharide, trehalose and isomaltose, or a combination thereof.

Description

Technical field:

[0001] The present invention relates to a composition comprising a methylxanthine in combination with a disaccharide derived from the enzymatic conversion of sucrose. More particularly, the present invention relates to a composition comprising a methylxanthine and a disaccharide derived from the enzymatic conversion of sucrose, the disaccharides being selected from the group consisting of turanose, leucrose, trehalulose and isomaltose, or a combination thereof. Background technology:

[0002] Methylated xanthines are part of foods, beverages and dietary supplements and are produced by a limited number of plant species, including tea (Camellia sinensis L, C. assamica var. kucha (green tea)), coffee (e.g., C. arabica, C. liberica, C. dewevrei, C. abeokut), cocoa (Theobroma cacao L.), cola nut (e.g., C. nitida), Paulownia (e.g., P. cupana), and Ilex (e.g., I. paraguarensis).

[0003] Natural products containing methylxanthines are frequently used in the food industry as dietary supplements, nutraceuticals, or nootropics as a direct result of their ability to enhance sustained and increased energy, mood and focus, improved memory, cognitive enhancement, better mind-muscle connection, performance enhancement, alertness, and increased fat burning potential.

[0004] The pharmacological activity of methylxanthines at the cellular level is attributed to their ability to prevent the neurotransmitter adenosine from binding to receptors in the brain, inhibit phosphodiesterases, block dopamine transporters, modulate GABA receptor action, and regulate intracellular calcium levels.

[0005] Methylxanthines are also known to act as psychostimulants, potent bronchodilators, enhance blood flow and prevent uric acid crystallization.

[0006] While several dietary supplements containing methylxanthines are available, there is a need to develop compositions comprising methylxanthines in combination with disaccharides derived from enzymatic conversion of sucrose to provide a blend of immediate release, delayed or extended release, sustained energy enhancers that will result in improved mood, focus, memory, alertness, cognitive enhancement, better mind-muscle connection, better performance, increased fat burning potential and information processing.

[0007] In addition to the above, it is also important to mask the bitter taste of methylxanthines by developing appropriate formulations.

[0008] Therefore, it is an object of the present invention to provide a composition comprising methylxanthines in combination with disaccharides derived from enzymatic conversion of sucrose, selected from the group consisting of turanose, leucrose, trehalulose and isomaltose, or mixtures thereof, in order to mask the bitter taste of the methylxanthines. Summary of the invention:

[0009] Accordingly, the present invention provides a composition comprising methylxanthines in an amount of 0.01% to 20% w / w and a disaccharide derived from the enzymatic conversion of sucrose in an amount of 10% to 90% w / w.

[0010] In one aspect, the methylxanthine is selected from caffeine, tecaine and methyllibericine, paraxanthine, theobromine, theophylline, alone or in combination, in an amount of 0.01% to 20% w / w.

[0011] In another aspect, the disaccharide derived from the enzymatic conversion of sucrose is selected from the group comprising turanose, leucrose, trehalulose and isomaltose, alone or in combination, in an amount of 10% to 90% w / w.

[0012] In a further aspect, the present invention provides a composition comprising individual methylxanthines selected from the group consisting of caffeine, tekaptone, paraxanthine, theobromine, theophylline and methyllibericine in an amount of 0.01% to 20% w / w in combination with disaccharides derived from enzyme-treated sucrose in an amount of 10% to 90% w / w and disaccharides selected from the group consisting of turanose, leucrose, trehalulose and isomaltose, alone or in combination.

[0013] In another aspect, the composition of the present invention may comprise a nutraceutical supplement, like a stilbenoid compound selected from resveratrol and pterostilbene, present in an amount of 0% to 20% w / w.

[0014] In another aspect, the composition of the present invention may comprise a suitable carrier or excipient or nutritional supplement in an amount of 0.01% to 20% w / w.

[0015] In another aspect, the composition of the present invention may comprise a nutraceutical excipient in an amount of 5%-90% w / w.

[0016] In yet another aspect, the present invention provides a process for preparing a composition comprising methylxanthines alone or in combination and a disaccharide derived from enzyme-treated sucrose, the process comprising:

[0017] i. adding methylxanthines in an amount of 0.01% to 20% w / w, alone or in combination, to an aqueous solution of enzymatically treated sucrose in an amount of 90% to 10% w / w;

[0018] ii. adding 0%-20% w / w amount of a stilbene compound such as pterostilbene, resveratrol to the solution of step (i);

[0019] iii. adding a nutraceutical excipient in an amount of 5% to 90% w / w to the solution of step (ii); and

[0020] iv. The solution of step (iii) was stirred at room temperature to avoid heat-induced conversion of sucrose to obtain the desired composition.

[0021] In one of these aspects, the compositions of the present invention can be formulated into various forms of nutritional supplements, such as powders, tablets, capsules, gel dosage forms, aqueous preparations, which contain caffeine, tecaine and methylliberic acid and various isomers of enzyme-treated sucrose, and these compositions can be used as central nervous system stimulants and metabolic stimulants. Specific implementation method:

[0022] The present invention will now be described in detail in its preferred and alternative embodiments so that various aspects thereof may be more clearly understood and appreciated.

[0023] Accordingly, the present invention discloses a composition comprising a methylxanthine in combination with a disaccharide derived from enzymatic conversion of sucrose, wherein the amount of methylxanthine is 0.01% to 20% w / w and the amount of disaccharide derived from enzymatic conversion of sucrose is 10% to 90% w / w.

[0024] In yet another embodiment, the methylxanthine is in its pure form or as a co-crystal or solvate, wherein the conformer / solvate is selected from the group comprising phenol, cinnamic acid, resveratrol, pterostilbene, alcohol, organic acid, and the like.

[0025] According to the present invention, the methylxanthine is selected from the group comprising caffeine, tecaine and methyllibericine, paraxanthine, theobromine, theophylline, or a combination thereof, in an amount of 0.01% to 20% w / w.

[0026] In another embodiment, the disaccharide derived from the enzymatic conversion of sucrose is selected from the group comprising turanose, leucrose, trehalulose and isomaltose, or a combination thereof, in an amount of 10% to 90% w / w.

[0027] In yet another embodiment, the present invention provides a composition comprising individual methylxanthines selected from the group consisting of caffeine, tecainine, paraxanthine, theobromine, theophylline and methyllibericine in an amount of 0.01% to 20% w / w in combination with disaccharides derived from enzyme-treated sucrose in an amount of 10% to 90% w / w and disaccharides selected from the group consisting of turanose, leucrose, trehalulose and isomaltose, alone or in combination thereof.

[0028] In another embodiment, the composition may comprise a nutraceutical supplement, such as a stilbene compound selected from resveratrol and pterostilbene, in an amount of 0% to 20% w / w.

[0029] In yet another embodiment, the composition may contain a suitable carrier or excipient or nutritional supplement in an amount of 0.01% to 20% w / w.

[0030] In another embodiment, the carrier or excipient or nutritional adjuvant is selected from the group including but not limited to: flavoring agents, coloring agents, viscosity modifiers, preservatives, chelating agents, antioxidants, surface modifiers and other nutritional adjuvants, alone or in combination.

[0031] In yet another embodiment, the composition may comprise the nutraceutical excipient in an amount of 5%-90% w / w.

[0032] In another embodiment, the nutraceutical excipients are selected from the group consisting of binders, diluents, lubricants, stabilizers, solubilizers, sustained release polymers, colorants, taste enhancers, and the like.

[0033] In yet another embodiment, the composition optionally comprises a bitter taste masking agent.

[0034] In another embodiment, the composition can be formulated as an oral solid, liquid or suspension.

[0035] In another embodiment, the composition can be formulated for oral administration in various forms of nutritional supplements such as powders, tablets, capsules, gel dosage forms, or aqueous formulations.

[0036] In another embodiment, the composition is provided as an aqueous composition.

[0037] In another embodiment, the present invention provides a process for preparing a composition comprising methylxanthines alone or in combination and disaccharides derived from enzyme-treated sucrose, the process comprising:

[0038] i. adding methylxanthines in an amount of 0.01% to 20% w / w, alone or in combination, to an aqueous solution of enzymatically treated sucrose in an amount of 90% to 10% w / w;

[0039] ii. adding 0%-20% w / w amount of a stilbene compound such as pterostilbene, resveratrol to the solution of step (i);

[0040] iii. adding a nutraceutical excipient in an amount of 5%-90% w / w to the solution of step (ii); and

[0041] iv. The solution of step (iii) was stirred at room temperature to avoid heat-induced conversion of sucrose to obtain the desired composition.

[0042] In another embodiment, a process for preparing a composition comprising methylxanthines alone or in combination and disaccharides derived from enzyme-treated sucrose, wherein the methylxanthines are selected from the group consisting of caffeine, tecaine, methyllibericine, paraxanthine, theobromine and theophylline; the disaccharides are selected from the group consisting of turanose, leucrose, trehalulose and isomaltose; suitable carriers or excipients or nutritional adjuvants are selected from the group consisting of flavoring agents, colorants, viscosity modifiers, preservatives, chelating agents, antioxidants, surface modifiers and other nutritional adjuvants; and the nutritional excipients are selected from the group consisting of binders, diluents, lubricants, stabilizers, solubilizers, sustained-release polymers, colorants, taste enhancers, etc.

[0043] In another embodiment, the composition of the present invention can be formulated into various forms of nutritional supplements, such as powders, tablets, capsules, gel dosage forms, aqueous preparations, which contain caffeine, tecaine and methylliberic acid and various isomers of enzyme-treated sucrose, and these compositions can be used as central nervous system stimulants and metabolic stimulants.

[0044] In yet another embodiment, the present invention provides compositions that can be used to significantly enhance sustained and increased energy, mood and attention, improve memory, cognitive enhancement, increase, maintain prolonged voluntary activity, performance enhancement, alertness, increase fat burning potential, increase stamina, reduce depression, impart beneficial hypoglycemic effects and alleviate sleep deprivation.

[0045] In another embodiment, the present invention provides compositions that can be used to significantly improve endurance, athletic performance, hunger reduction and weight loss, as well as inflammation and pain reduction, for preventive and curative treatment of neurological diseases, learning performance, mood enhancement, alertness, uric acid reduction and management.

[0046] In yet another embodiment, the composition provides a delayed or extended release composition.

[0047] In another embodiment, the present invention provides a method of significantly stimulating the central nervous system and metabolizing stimulants in a subject, wherein the method comprises providing to the subject a composition comprising a nutritionally effective amount of a methylxanthine in combination with a disaccharide derived from the enzymatic conversion of sucrose.

[0048] In another embodiment, the present invention provides a method for significantly improving endurance, athletic performance, hunger reduction and weight loss, as well as inflammation and pain reduction in a subject, for preventive and curative treatment of neurological diseases, learning performance, mood enhancement, alertness, uric acid reduction and management, wherein the method comprises providing to the subject a composition comprising a nutritionally effective amount of a methylxanthine in combination with an enzymatically converted disaccharide derived from sucrose.

[0049] In another embodiment, the present invention provides a method of significantly enhancing sustained and increased energy, mood and attention, improving memory, cognitive enhancement, increasing, maintaining extended locomotor activity, performance enhancement, alertness, increasing fat burning potential, increasing endurance, reducing depression, imparting beneficial hypoglycemic effects, and alleviating sleep deprivation in a subject, wherein the method comprises providing to the subject a composition comprising a nutritionally effective amount of a methylxanthine in combination with an enzymatically converted disaccharide derived from sucrose.

[0050] In one embodiment, the present invention provides compositions suitable for oral administration to mammalian subjects, including but not limited to humans, comprising caffeine, tecaine, and methyllibericine in solid or liquid dosage form.

[0051] According to another embodiment, the total concentration of caffeine, tecaine and methyl liberine in the composition is in the range of 0.01% to 20% by weight based on the total weight of the composition, wherein the remaining weight mainly contains disaccharides derived from enzyme-treated sucrose isomers, alone or in combination, which are provided in a solid or liquid dosage form using a suitable carrier or excipient or nutritional adjuvant.

[0052] The total amount of methylxanthines in the enzymatically treated sucrose solution was maintained between 0.01% and 20%.

[0053] To achieve stability, solubility and taste, appropriate food grade preservatives, viscosity modifiers and optionally bitter taste masking agents like stilbenoids, eg, resveratrol, pterostilbene are added to the formulation.

[0054] The compositions of the present invention provide significant improvements in endurance, athletic performance, hunger reduction and weight loss, as well as inflammation and pain reduction, preventive and curative treatment for neurological diseases, learning performance, mood enhancement, alertness, uric acid reduction and management.

[0055] The compositions of the present invention also provide debittering of methylxanthines due to their ability to form complexes with the glucose portion of the disaccharide.

[0056] Since the breakdown of the treated disaccharide compound requires a longer metabolic time than untreated sucrose or glucose, the composition further provides slow metabolism of caffeine and a low glycemic index, which results in a delayed or extended release of a long-lasting energy enhancer.

[0057] These compositions and preparation processes are further described by the following non-limiting examples, which provide preferred modes for carrying out the processes of the present invention. It should be understood that several changes, modifications, optimizations, alternations of the processes described herein are fully within the scope of those skilled in the art, and such changes, modifications, optimizations, alternations, etc. should be interpreted as being within the scope of the inventive concept as disclosed anywhere in the specification.

[0058] Illustrative formulations:

[0059] The formulations listed below are set forth for illustrative purposes only and should not be used in any way to limit the proper interpretation of the claims. In the formulations, the nutraceutical excipient percentages vary between 5%-90% w / w.

[0060] An illustrative formulation is set forth below:

[0061] Table 1: Formulations of methylxanthines with disaccharides derived from enzymatic conversion of sucrose

[0062]

[0063]

[0064] Table 2: Formulations of methylxanthines with disaccharides derived from enzymatic conversion of sucrose

[0065]

[0066]

[0067] General procedure for the preparation of formulations of methylxanthines with sucrose isomers

[0068] Methylxanthines (caffeine, tekatanin, methylliberine, paraxanthine, theobromine, theophylline or a combination thereof: 0.01% to 20% w / w) are added to an aqueous solution (90%-10% w / w) of enzyme-treated sucrose isomers (turanose, leucrose, trehalulose, and isomaltose, or a combination thereof), followed by stilbenoids like resveratrol (0%-20% w / w), pterostilbene (0%-20% w / w) and nutraceutical excipients like binders, diluents, lubricants, stabilizers, solubilizers, slow-release polymers, suitable colorants, taste enhancers, etc. (5%-90% w / w). The composition is stirred at room temperature for 1.0-2.0 h to avoid heat-induced conversion of sucrose. The resulting solution / suspension is packaged for use.

[0069] Example 1:

[0070] 12.5 g of trehalulose and 12.5 g of isomaltose were added to 100 ml of purified water under stirring at room temperature. Caffeine 150 mg, tekatanine 100 mg and methyl libericidal base: 50 mg were slowly added and allowed to stir for 30 minutes, followed by the addition of 5 g of calcium stearate. The resulting solution was stirred at room temperature for 2-3 h.

[0071] Example 2:

[0072] 12.5 g of turanose and 12.5 g of leucrose were added to 100 ml of purified water under stirring at room temperature. Caffeine 150 mg, tekatanine 50 mg and methyl libericidal: 100 mg were slowly added and allowed to stir for 30 minutes, followed by the addition of 5 g of calcium stearate. The resulting solution was stirred at room temperature for 2-3 h.

[0073] Example 3:

[0074] 25g of trehalulose was added to 100ml of purified water under stirring at room temperature. Caffeine 150mg, tekatanine 100mg and methyl libericidal base: 50mg were slowly added and allowed to stir for 30 minutes, followed by addition of 500mg of pterostilbene and 5g of calcium stearate. The resulting solution was stirred at room temperature for 2-3h.

[0075] Example 4:

[0076] 25g of trehalulose was added to 100ml of purified water under stirring at room temperature. Caffeine 150mg, tekatanine 100mg and methyl libericidal base: 50mg were slowly added and allowed to stir for 30 minutes, followed by the addition of 300mg of pterostilbene and 5g of calcium stearate. The resulting solution was stirred at room temperature for 2-3h.

[0077] Example 5:

[0078] 12.5 g turanose and 12.5 g leucrose were added to 100 ml purified water under stirring at room temperature. Caffeine 150 mg, tekatanine 50 mg and methyl libericidal: 100 mg were slowly added and allowed to stir for 30 minutes, followed by the addition of 500 mg resveratrol and 5 g calcium stearate. The resulting solution was stirred at room temperature for 2-3 h.

[0079] Although the present invention has been described in detail above for purposes of illustration, it should be understood that such details are for that purpose only and variations may be made therein by those skilled in the art without departing from the spirit and scope of the present invention, except as it may be limited by the claims.

Claims

1. A composition comprising a combination of methylxanthines and disaccharides derived from the enzymatic conversion of sucrose, wherein the amount of the methylxanthines is 0.01% to 20% w / w and the amount of disaccharides derived from the enzymatic conversion of sucrose is 10% to 90% w / w.

2. The composition according to claim 1, wherein These methylxanthines are in their pure form or as co-crystals or solvates.

3. The composition according to claim 2, wherein The conformer / solvate is selected from the group consisting of phenol, cinnamic acid, resveratrol, pterostilbene, alcohol, organic acid, and the like.

4. The composition according to claims 1 and 2, wherein The methylxanthines are selected from the group comprising caffeine, tecaine, methyllibericine, paraxanthine, theobromine, theophylline, alone or in combination, in an amount of 0.01% to 20% w / w.

5. The composition according to claim 1, wherein The disaccharide derived from the enzymatic conversion of sucrose is selected from the group comprising turanose, leucrose, trehalulose and isomaltose, alone or in combination, in an amount of 10% to 90% w / w.

6. The composition according to claim 1, wherein The composition may comprise a nutraceutical supplement selected from stilbenes in an amount of 0% to 20% w / w.

7. The composition according to claim 6, wherein The stilbene compounds are selected from resveratrol and pterostilbene.

8. The composition of claim 1, wherein The composition comprises a suitable carrier or excipient or nutritional supplement in an amount of 0.01% to 20% w / w.

9. The composition of claim 8, wherein These carriers or excipients or nutritional adjuvants are selected from the group including but not limited to: flavoring agents, coloring agents, viscosity modifiers, preservatives, chelating agents, antioxidants, surface modifiers and other nutritional adjuvants, alone or in combination.

10. The composition according to claim 1, wherein The composition may comprise a nutraceutical excipient in an amount of 5% to 90% w / w.

11. The composition according to claim 10, wherein These nutraceutical excipients are selected from the group comprising binders, diluents, lubricants, stabilizers, solubilizers, sustained release polymers, colorants, taste enhancers and the like.

12. The composition of claim 1, wherein The composition comprises a combination of individual methylxanthines selected from the group consisting of caffeine, tekaptanine, paraxanthine, theobromine, theophylline or methyllibericrine in an amount of 0.01%-20% w / w and disaccharides selected from the group consisting of turanose, leucrose, trehalulose and isomaltose, alone or in combination, in an amount of 10%-90% w / w.

13. The composition of claim 1, wherein The composition optionally comprises a bitter taste masking agent.

14. The composition according to any one of claims 1 to 13, wherein The composition may be formulated as a solid, liquid or suspension for oral administration.

15. The composition according to any one of claims 1 to 13, wherein The composition may be formulated for oral administration in various forms of nutritional supplements such as powders, tablets, capsules, gel dosage forms or aqueous formulations.

16. The composition of claims 1 to 13, wherein The composition is provided as an aqueous composition.

17. A process for preparing a composition comprising methylxanthines alone or in combination and disaccharides derived from enzyme-treated sucrose, the process comprising: i. adding methylxanthines in an amount of 0.01% to 20% w / w, alone or in combination, to an aqueous solution of enzymatically treated sucrose in an amount of 90% to 10% w / w; ii. adding 0% to 20% w / w of the amount of stilbene compound to the solution of step (i); iii. adding 5%-90% w / w of the nutritional excipient to the solution of step (ii); as well as iv. The solution of step (iii) is stirred at room temperature to avoid heat-induced conversion of sucrose to obtain the desired composition.

18. The process of claim 17, wherein: These methylxanthines are selected from the group including the following items: caffeine, tekaptanine, methylliberine, paraxanthine, theobromine and theophylline; disaccharides are selected from the group including the following items: turanose, leucrose, trehalulose and isomaltose; suitable carriers or excipients or nutritional adjuvants are selected from the group including the following items: flavoring agents, colorants, viscosity regulators, preservatives, chelating agents, antioxidants, surface modifiers and other nutritional adjuvants; and nutritional product excipients are selected from the group including the following items: binders, diluents, lubricants, stabilizers, solubilizers, sustained-release polymers, colorants, taste enhancers, etc.

19. A composition as claimed in any one of claims 1 to 18, which is useful as a central nervous system stimulant and a metabolic stimulant.

20. A composition as claimed in any one of the preceding claims 1 to 18, which can be used to enhance sustained and increased energy, mood and attention, improve memory, cognitive enhancement, increase, maintain prolonged voluntary activity, performance enhancement, alertness, increase fat burning potential, increase endurance, reduce depression, impart beneficial hypoglycemic effects and alleviate sleep deprivation.

21. A composition as described in any one of the preceding claims 1 to 18, which can be used to improve endurance, athletic performance, hunger reduction and weight loss, as well as inflammation and pain reduction, for preventive and curative treatment of neurological diseases, learning performance, mood enhancement, alertness, uric acid reduction and management.

22. A composition as claimed in any one of claims 1 to 21, wherein The composition provides a delayed or extended release composition.

23. A method of stimulating the central nervous system and metabolizing a stimulant in a subject, wherein: The method comprises providing to the subject a nutritionally effective amount of a composition as claimed in any one of the preceding claims comprising a methylxanthine in combination with a disaccharide derived from enzymatic conversion of sucrose.

24. A method of improving endurance, athletic performance, hunger reduction and weight loss, and inflammation and pain reduction in a subject, for preventive and curative treatment of neurological diseases, learning performance, mood enhancement, alertness, uric acid reduction and management, wherein: The method comprises providing to the subject a nutritionally effective amount of a composition as claimed in any one of the preceding claims comprising a methylxanthine in combination with a disaccharide derived from enzymatic conversion of sucrose.

25. A method of enhancing sustained and increased energy, mood and attention, improving memory, cognitive enhancement, increasing, maintaining extended voluntary activity, performance enhancement, alertness, increasing fat burning potential, increasing stamina, reducing depression, imparting beneficial hypoglycemic effects, and alleviating sleep deprivation in a subject, wherein: The method comprises providing to the subject a nutritionally effective amount of a composition as claimed in any one of the preceding claims comprising a methylxanthine in combination with a disaccharide derived from enzymatic conversion of sucrose.

Images