Novel nutraceutical / therapeutic compositions of cinnamic acid derivatives and sucrose isomers

Abstract

The present invention discloses a dietary supplement / therapeutic composition comprising cinnamic acid derivatives and sucrose isomers useful as nootropic performance enhancers and for pain management. The present invention further discloses a method for preparing said composition and a method for its use.

Description

[Technical field]

[0001] The present invention relates to dietary supplement / therapeutic compositions comprising cinnamic acid derivatives and sucrose isomers, useful as nootropic performance enhancers and for pain management. The present invention further relates to methods for preparing said compositions and methods of use thereof. [Background technology]

[0002] Hydroxycinnamic acids are phenolic acid compounds present in many plants either in the free state or as derivatives such as esters or amides, and are also known to have potent antioxidant, antitumor, antidepressant, cytoprotective neuroinflammatory, anti-inflammatory and anti-arthritic properties in neurodegenerative diseases. They also prevent insulin resistance, cardiovascular disease, renal dysfunction, diabetes, dyslipidemia and improve liver function. Furthermore, esters of hydroxycinnamic acids have potential therapeutic applications in experimental diabetes and hyperlipidemia, lowering lipid profiles, improving brain function and pain management.

[0003] Naturally occurring esters of hydroxycinnamic acids are known to reduce anxiety and stress by modulating GABA receptors. Cinnamic acid esters are known to increase neuronal firing, leading to improved brain function and memory. WO2020176432 discloses a method for inhibiting the progression of glycine encephalopathy, comprising administering to a patient in need thereof a pharmaceutical composition comprising a therapeutically effective amount of cinnamic acid.

[0004] China Patent Publication No. 107624068 discloses a method for treating hypertension using a combination containing cinnamic acid and zinc in an individual in need thereof.

[0005] Sugar isomers also participate in various metabolic and signaling pathways, including those that contribute to their effectiveness as neuroprotectants, antioxidant properties, scavengers of hydroxyl radicals, and against inflammation. These sugars also have many physiological and cardiometabolic benefits, from weight loss to improved glycemic control and reduced insulin resistance. Health benefits of rare sugars in humans are beginning to emerge for several rare sugars, including allulose, tagatose, isomaltulose, arabinose, and trehalose.

[0006] Currently, the naturally occurring sucrose isomers trehalose, trehalulose, turanose, leucrose, and isomaltulose are considered to be possible substitutes for sucrose due to their potential cognitive benefits such as positive effects on mood, improved episodic and working memory, improved attention speed, etc. In addition, sucrose isomers also contribute to fat oxidation in energy metabolism; improved physical performance; and protection against hypoglycemia during exercise.

[0007] The evidence of facilitation of episodic memory suggests a specific enhancing effect of sucrose isomer ingestion on cognitive domains related to hippocampal function. In support of this, facilitation effects have also been reported for additional hippocampal-dependent cognitive functions such as recognition memory, visuospatial memory and visuospatial function.

[0008] The antioxidant activity of the rare sugar D-allose by scavenging hydroxyl radicals has been recently reported, and its effect is close to that of D-glucose in scavenging hydroxyl radicals. Cancer and tumor inhibition is considered to be the most important property of D-allose. D-allose has been reported to be effective against various human cancers, such as ovarian, cervical and skin cancer, hepatocellular and prostate cancer. Leukemia, head and neck cancer, pancreatic and lung cancer are also inhibited by D-allose.

[0009] The antioxidant activity of D-allulose persists over long periods of storage and is highly soluble compared to D-fructose or D-glucose. D-allulose has shown hypoglycemic properties and therapeutic effects on type 2 diabetes. It also has anti-obesity and anti-hyperlipidemic effects. Furthermore, D-allulose can be used as a neuroprotectant against inflammation and atherosclerotic diseases.

[0010] D-tagatose has antioxidant and cryoprotective properties in addition to its ability to aid in weight loss.D-tagatose also has therapeutic potential in type 2 diabetes management as it improves glycemic control.

[0011] Although the applications of rare sugars in human nutrition and medicine have been widely studied, their potential use for sustainable food production, and applications in agriculture, have been hardly reported.

[0012] Despite the potential benefits of these natural products, there is hardly any literature available in the prior art or any products available in the market for human use that offer the synergistic properties of cinnamic acid with isomers of common sugars, particularly sucrose.

[0013] Therefore, providing compositions comprising a combination of cinnamic acid and its derivatives with sugar isomers is an object of the present invention due to their structural diversity and unique and remarkable pharmacological and pharmacodynamic actions such as antidepressant, anticancer, antioxidant, anti-inflammatory and antiviral activities.

[0014] Thus, the inventors felt that there is a need in the art to develop novel formulation(s) that help improve concentration and learning, reduce anxiety, improve physical and mental performance, effectively manage inflammatory diseases and pain, and also act as scavengers of reactive oxygen species, thereby providing cytoprotection. [Prior art documents] [Patent documents]

[0015] [Patent Document 1] International Publication No. 2020176432 Brochure [Patent Document 2] China Patent Application Publication No. 107624068 Summary of the Invention [Means for solving the problem]

[0016] In accordance with the above objectives, the present invention provides a unique dual role of novel dietary supplements / therapeutic compositions / formulations useful as nootropic performance enhancers comprising cinnamic acid or a derivative thereof and sucrose isomers.

[0017] Thus, the present invention provides a novel composition / formulation having nutritional / therapeutic value comprising a cinnamic acid derivative and a sucrose isomer, wherein the cinnamic acid or its derivative is present in an amount of 2%-90% w / w and the sucrose isomer is present in an amount of 10-90% w / w.

[0018] In another aspect, the composition also contains suitable excipients which may be selected from the group consisting of binders, diluents, lubricants, stabilizers, solubilizers, sustained release polymers, suitable colorants, taste enhancers, etc. to obtain the desired formulation properties.

[0019] In further aspects, the dietary supplement / therapeutic composition can be formulated using appropriate excipients into either oral solid, liquid or suspension formulations using appropriate techniques.

[0020] In yet another aspect, the present invention provides a method for improving concentration and learning, reducing anxiety, improving physical and mental performance, effectively managing inflammatory diseases and pain, scavenging reactive oxygen species, and thereby providing cytoprotection in a subject, comprising treating said subject with a composition comprising a therapeutically effective amount of cinnamic acid or a derivative thereof and a sucrose isomer. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] The present invention will now be described in detail in connection with certain preferred and optional embodiments so that the various aspects thereof may be more fully understood and appreciated.

[0022] Thus, the present invention provides novel dietary supplements / therapeutic compositions / formulations comprising cinnamic acid or a derivative thereof and sucrose isomers useful as nootropic performance enhancers and for pain management.

[0023] The term "nutraceutical" refers to a portmanteau of "nutrition" and "pharmaceutical." Nutraceuticals are generally part of "functional foods" or foods that play an important role in modifying and maintaining normal physiological functions that sustain human health.

[0024] Thus, the present invention provides a novel dietary supplement composition / formulation having nutritional / therapeutic value comprising a cinnamic acid derivative and a sugar isomer, wherein the cinnamic acid or derivative thereof is present in an amount of 2%-90% w / w, the sucrose isomer is present in an amount of 10-90% w / w, and the dietary supplement / therapeutic excipient is present in an amount of 5-90%.

[0025] In another embodiment, the dietary supplement / therapeutic compositions of the present invention may also be useful in pain management.

[0026] In one embodiment, the cinnamic acid derivative is selected from hydroxycinnamic acids, their esters and amides.

[0027] In one embodiment, the hydroxycinnamic acid derivative (CA) is selected from hydroxycinnamic acid, ferulic acid, caffeic acid, sinapic acid, chlorogenic acid, rosmarinic acid, syringic acid, p-coumaric acid, and the like.

[0028] In another embodiment, the derivatives of cinnamic acid esters are selected from alkyl / aralkyl alcohols esterified with suitable cinnamic acids having the general formula CA-CO-OR, where CA=cinnamic acid and R=C1-C22 alkyl chain; Ph-CH2CH2- and CA-CO-O(CH)nO-CO-CA, where n=1-10. Esters of cinnamic acid also include branched alkyl groups such as isopropyl, iso-butyl cinnamate, isopentyl, phenylethyl, etc.

[0029] In yet another embodiment, the derivative of cinnamic acid amide is selected from amides having the general formula CA-CO-NHR, where CA-CO-=cinnamic acid and NHR=tyramine, phenethylamine, serotonin or dopamine.

[0030] In another embodiment, the sugar isomer is selected from monosaccharides or disaccharides. The monosaccharide sugar isomer is selected from D-allose, D-allulose and D-tagatose.

[0031] The disaccharide isomers are selected from trehalulose, turanose, leucrose and isomaltulose.

[0032] In another embodiment, the composition also contains suitable dietary supplement / therapeutic excipients which may be selected from the group consisting of binders, diluents, lubricants, stabilizers, solubilizers, slow release polymers, suitable colorants, taste enhancers, etc.

[0033] In a further embodiment, the composition may be formulated into either an oral solid, liquid or suspension formulation using suitable excipients.

[0034] In another embodiment, the dietary supplement / therapeutic composition of the present invention may be prepared by methods known in the art, including adding appropriate excipients to sucrose isomers together with the active ingredient cinnamic acid derivatives in appropriate ratios.

[0035] Thus, the method for the preparation of the composition comprises: i. adding a cinnamic acid derivative in an amount of 2%-90% w / w to an aqueous solution of a sugar isomer in an amount of 10%-90% w / w; ii. adding a suitable nutraceutical excipient in an amount of 5-90% w / w to the solution of step (i); and iii. agitating the solution of step (ii) to avoid heat-induced inversion of the sucrose, followed by drying to obtain the desired composition; Includes.

[0036] In yet another embodiment, the present invention provides a method for enhancing brain performance, reducing anxiety, and improving learning and concentration without anxiety in a subject, comprising treating said subject with a composition comprising a dietary supplement effective amount of cinnamic acid or a derivative thereof and a sucrose isomer.

[0037] In yet another embodiment, the present invention provides a method of treating inflammation in a subject, comprising treating the subject having inflammation selected from COX 2 associated inflammation with a composition comprising a therapeutically effective amount of cinnamic acid or a derivative thereof and a sucrose isomer.

[0038] The term "nutraceutical effective amount" means an amount that provides the desired nutritional and therapeutic benefit of the outcome in alleviating or reducing or controlling the progression of a disease.

[0039] The following examples are presented to further illustrate the invention using experimental conditions, which are purely illustrative and are not intended to limit the scope of the invention.

[0040] [Example] Exemplary Formulations: The formulations listed below are provided for illustrative purposes only and should not be used to limit the proper construction of the claims in any manner. In the formulations, the percentage of dietary supplement excipients varies from 5 to 90%. Exemplary formulations are shown below: [Example 1] Preparations of cinnamic acid derivatives with mono- and disaccharides [Table 1]

[0041] TIFF2025511120000002.tif163159 [Example 2] Preparations of cinnamic acid ester derivatives with mono- and disaccharides [Table 2]

[0042] TIFF2025511120000004.tif232159

[0043] TIFF2025511120000005.tif231159

[0044] TIFF2025511120000006.tif160158 [Example 3] Formulations of cinnamic acid amide derivatives with mono- and disaccharides [Table 3]

[0045] TIFF2025511120000008.tif230157

[0046] TIFF2025511120000009.tif213159

[0047] [Example 4] General procedure for preparing formulations of cinnamic acid derivatives and sucrose isomers To aqueous solutions of D-allose, D-allulose and D-tagatose, L-arabinose, trehalulose, turanose, leucrose and isomaltulose (90-10% w / w), cinnamic acids / esters / amides (2-90% w / w) were added, followed by appropriate nutraceutical excipients (5-90% w / w). The compositions were stirred at room temperature for 1.0-2.0 h to avoid heat-induced inversion of sucrose. The resulting solutions / suspensions were packaged for use.

[0048] [Example 4a] 25 g of trehalulose was added to 100 mL of purified water at room temperature with stirring. 0.1 g of n-docosyl coumarate was slowly added and stirred for 30 minutes, followed by 5 g of calcium stearate. The resulting solution was stirred at room temperature for 1 hour and dried.

[0049] Example 4b 25 g of isomaltulose was added to 100 mL of purified water with stirring at room temperature. 0.5 g of n-octadecyl ferulate was slowly added and stirred for 30 minutes, followed by 5 g of calcium stearate. The resulting solution was stirred at room temperature for 1 hour and evaporated to dryness.

[0050] [Example 4c] 25 g of D-allulose was added to 100 mL of purified water with stirring at room temperature. 1 g of n-trans-caffeoyltyramine was slowly added and stirred for 30 minutes, followed by the addition of 5 g of calcium stearate. The resulting solution was stirred at room temperature for 1 hour and freeze-dried.

Claims

1. A composition having nutritional / therapeutic value comprising a cinnamic acid derivative and a sucrose / sugar isomer, wherein the cinnamic acid derivative is present in an amount of 2%-90% w / w and the sucrose / sugar isomer is present in an amount of 10-90% w / w.

2. 10. The composition of claim 1 comprising a dietary supplement / therapeutic excipient in an amount of 5-90%.

3. The composition of claim 1 , wherein the cinnamic acid derivative is selected from hydroxycinnamic acids, their esters and amides.

4. The composition according to claim 3, wherein said hydroxycinnamic acid derivative (CA) is selected from hydroxycinnamic acid, ferulic acid, caffeic acid, sinapic acid, chlorogenic acid, syringic acid, p-coumaric acid, etc.

5. The cinnamic acid ester derivatives have the general formula CA-CO-OR, where CA represents cinnamic acid and R represents a C1-C22 alkyl chain, Ph-CH ２ CH ２ 4. The composition of claim 3, wherein the ester is selected from alkyl / aralkyl alcohols esterified with cinnamic acid having the formula: CA-CO-O(CH)nO-CO-CA (wherein n=1-10), said esters of cinnamic acid including branched alkyl groups such as isopropyl, iso-butyl cinnamate, isopentyl, etc.

6. 4. The composition according to claim 3, wherein the derivative of cinnamic acid amide is selected from amides having the general formula CA-CO-NHR, where CA represents cinnamic acid and NHR represents tyramine, serotonin, dopamine, phenethylamine.

7. The composition of claim 1 , wherein the sugar isomer is selected from a monosaccharide or a disaccharide.

8. The composition of claim 7, wherein the monosaccharide isomer is selected from D-allose, D-allulose and D-tagatose.

9. The composition of claim 7, wherein the disaccharide isomer is selected from trehalulose, turanose, leucrose and isomaltulose.

10. 3. The composition of claim 2, which may contain dietary supplement / therapeutic excipients selected from the group consisting of binders, diluents, lubricants, stabilizers, solubilizers, sustained release polymers, colorants, taste enhancers, and the like.

11. 11. The composition of any one of claims 1 to 10, which may be formulated as either an oral solid, liquid or suspension.

12. A composition comprising a cinnamic acid derivative according to any one of claims 1 to 11 and a sucrose isomer as a dietary supplement / therapeutic composition.

13. A method for the preparation of a composition comprising the steps of: i. adding a cinnamic acid derivative in an amount of 2% to 90% w / w to an aqueous solution of sugar isomers in an amount of 10% to 90% w / w; ii. adding a suitable nutraceutical excipient in an amount of 5-90% w / w to the solution of step (i); and iii. The solution of step (ii) is stirred to avoid heat-induced inversion of the sucrose, followed by drying to obtain the desired composition. A method comprising:

14. A method for improving brain performance, reducing anxiety, and improving learning and concentration without anxiety in a subject, comprising providing to the subject a dietary supplement effective amount of a composition comprising cinnamic acid or a derivative thereof described in any one of claims 1 to 13 and a sucrose isomer.

15. A method for treating inflammation in a subject, comprising providing to the subject a therapeutically effective amount of a composition comprising cinnamic acid or a derivative thereof according to any one of claims 1 to 14 and a sucrose isomer, wherein the inflammation is selected from inflammation associated with COX 2.

16. A composition comprising a cinnamic acid derivative according to any one of claims 1 to 15 and a sucrose isomer for enhancing brain performance, reducing anxiety, and improving learning and concentration without anxiety.

17. A composition for treating inflammation, comprising a cinnamic acid derivative according to any one of claims 1 to 16 and a sucrose isomer, wherein the inflammation is selected from inflammation associated with COX 2.

18. A composition comprising a cinnamic acid derivative according to any one of claims 1 to 17 and a sucrose isomer, useful as a nootropic performance enhancer and for pain management.

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