Novel health-care / treatment composition of cinnamic acid derivative and sucrose isomer

Abstract

Healthcare / therapeutic compositions comprising cinnamic acid derivatives and sucrose isomers are disclosed, which can be used as smart enhancers, as well as for pain management. Methods of making the compositions and methods of using the same are also disclosed.

Description

Technical field:

[0001] The present invention relates to a health care / therapeutic composition comprising cinnamic acid derivatives and sucrose isomers, which can be used as an intelligence enhancer and can also be used for pain management. The present invention also relates to a method for preparing the composition and a method of using the composition.

[0002] Background of the invention and prior art:

[0003] Hydroxycinnamic acids are phenolic acid compounds that are present in many plants in the free state or in the form of derivatives such as esters or amides and are known to have potent antioxidant, antitumor, antidepressant, cytoprotective neuroinflammatory in neurodegenerative diseases, anti-inflammatory and anti-arthritic properties. They can also prevent insulin resistance, cardiovascular disease, renal dysfunction, diabetes, dyslipidemia and improve liver function. In addition, hydroxycinnamic acid esters have potential therapeutic uses in experimental diabetes and hyperlipidemia, reducing blood lipid levels, improving brain function and pain management.

[0004] Natural hydroxycinnamate is known to reduce anxiety and stress by regulating GABA receptors. Cinnamate is known to increase the firing of neurons, thereby improving brain function and memory. WO2020176432A1 discloses a method for inhibiting the progression of glycine encephalopathy, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising cinnamic acid to a patient in need thereof.

[0005] CN107624068A discloses a method of treating hypertension in an individual in need thereof using a combination comprising cinnamic acid and zinc.

[0006] Isomers of sugars are also involved in various metabolic and signaling pathways, including those that contribute to antioxidant properties, hydroxyl radical scavengers, anti-inflammatory effects, and as neuroprotectants. These sugars also have many physiological and cardiometabolic benefits, including weight loss, improved glycemic control, and reduced insulin resistance. Several rare sugars have been found to have health benefits in humans, including allulose, tagatose, isomaltulose, arabinose, and trehalose.

[0007] Currently, the natural sucrose isomers, trehalose, trehalulose, turanose, leucrose, and isomaltulose are considered as possible substitutes for sucrose because of their potential cognitive benefits, such as positive effects on mood, improved episodic and working memory, and increased speed of concentration. In addition, sucrose isomers also contribute to fat oxidation in energy metabolism; improve physical function; and prevent hypoglycemia during exercise.

[0008] Evidence for enhancing episodic memory suggests that sucrose isomer ingestion has specific enhancing effects on cognitive areas associated with hippocampal function. In support of this, it has also been reported to have facilitatory effects on other hippocampal-dependent cognitive functions such as recognition memory, visuospatial memory, and visuospatial function.

[0009] Recently, it has been reported that the rare sugar D-allose has antioxidant activity by eliminating hydroxyl radicals, and its effect is close to the extent that D-glucose scavenges hydroxyl radicals. Cancer and tumor suppression are considered to be the most important properties of D-allose. D-allose is reported to be effective against various human cancers, such as ovarian cancer, cervical cancer and skin cancer, hepatocellular carcinoma, and prostate cancer. D-allose also inhibits leukemia, head and neck cancer, pancreatic cancer, and lung cancer.

[0010] The antioxidant activity of D-psicose persists upon long-term storage and is highly soluble compared to D-fructose or D-glucose. D-psicose exhibits hypoglycemic properties and therapeutic effects on type 2 diabetes. It also has anti-obesity and anti-hyperlipidemic effects. In addition, D-psicose can be used as a neuroprotectant against inflammatory and atherosclerotic diseases.

[0011] In addition to aiding in weight loss, D-tagatose has antioxidant and antifreeze protective properties. D-tagatose also has therapeutic potential in the management of type 2 diabetes as it can improve glycemic control.

[0012] Although rare sugars have been extensively studied for their applications in human nutrition and medicine, their potential uses in sustainable food production and agricultural applications have been less reported.

[0013] Despite the potential benefits of these natural products, there is virtually no prior art literature or commercially available products for human use that possess the synergistic properties of cinnamic acid and sugar isomers, particularly sucrose isomers.

[0014] Therefore, it is an object of the present invention to provide a composition comprising a combination of cinnamic acid and its derivatives and sugar isomers because they have structural diversity, and unique and significant pharmacological and pharmacodynamic effects, such as antidepressant, anticancer, antioxidant, anti-inflammatory and antiviral activities.

[0015] Therefore, the inventors believe that there is a need in the art to develop new formulations to help improve concentration and learning ability, reduce anxiety, improve physical and mental performance, effectively control inflammatory diseases and pain, and act as scavengers of reactive oxygen species, thereby providing cell protection. SUMMARY OF THE INVENTION

[0017] According to the above objects, the present invention provides a novel health care / therapeutic composition / preparation having a unique dual effect, which comprises cinnamic acid or its derivatives and sucrose isomers and can be used as an intelligence enhancer.

[0018] Therefore, the present invention provides a novel composition / preparation with nutritional / therapeutic value, which comprises cinnamic acid derivatives and sucrose isomers, wherein the content of cinnamic acid or its derivatives is 2%-90% w / w, and the content of sucrose isomers is 10-90% w / w.

[0019] On the other hand, the composition further contains appropriate excipients, which can be selected from binders, diluents, lubricants, stabilizers, solubilizers, sustained-release polymers, appropriate colorants, flavor enhancers, etc., to obtain the desired preparation properties.

[0020] On the other hand, the health care / therapeutic composition can be formulated into oral solid, liquid or suspension preparations using suitable excipients and suitable techniques.

[0021] In another aspect, the present invention provides a method for improving concentration and learning ability, reducing anxiety, improving physical and mental performance, effectively controlling inflammatory diseases and pain, and scavenging reactive oxygen species to provide cell protection in an individual, the method comprising treating the individual with a composition comprising a therapeutically effective amount of cinnamic acid or a derivative thereof and a sucrose isomer. Detailed description of the invention:

[0023] The invention will now be described in detail in conjunction with certain preferred and alternative embodiments in order to more fully understand and appreciate its various aspects.

[0024] Thus, the present invention provides novel health / therapeutic compositions / formulations comprising cinnamic acid or its derivatives and sucrose isomers, which are useful as intelligence enhancers and also for pain management.

[0025] The term "nutraceutical" refers to the combination of "nutrition" and "drug". In a broad sense, nutraceuticals are part of "functional foods" or "foods that play an important role in changing and maintaining normal physiological functions that maintain human health."

[0026] Therefore, the present invention provides a new health care composition / formulation, which comprises cinnamic acid derivatives and sugar isomers with nutritional / therapeutic value, wherein the content of cinnamic acid or its derivatives is 2%-90% w / w, the content of sucrose isomers is 10-90% w / w, and the content of health care / therapeutic excipients is 5-90%.

[0027] In another aspect, the healthcare / therapeutic composition of the present invention can also be used for pain management.

[0028] In one embodiment, the cinnamic acid derivative is selected from hydroxycinnamic acid, esters and amides thereof.

[0029] 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.

[0030] In another embodiment, the cinnamate derivatives are selected from alkyl / aralkyl alcohols esterified with appropriate cinnamic acid, with the general formula CA-CO-OR, wherein CA = cinnamic acid, R = C1-C22 alkyl chain; Ph-CH2CH2- and CA-CO-O(CH)nO-CO-CA, wherein n = 1-10. Cinnamate also includes branched alkyl groups, such as isopropyl, isobutyl cinnamate, isopentyl, phenethyl, etc.

[0031] In yet another embodiment, the cinnamic acid amide derivative is selected from amides having the general formula CA-CO-NHR, wherein CA-CO-=cinnamic acid, NHR=tyramine, phenethylamine, serotonin or dopamine.

[0032] In yet another embodiment, the isomer of the sugar is selected from a monosaccharide or a disaccharide. The isomer of the monosaccharide is selected from D-allose, D-psicose and D-tagatose.

[0033] The isomers of the disaccharide are selected from trehalose, turanose, leucrose and isomaltulose.

[0034] In another embodiment, the composition further contains suitable health care / therapeutic excipients, which can be selected from binders, diluents, lubricants, stabilizers, solubilizers, sustained release polymers, appropriate colorants, flavor enhancers, and the like.

[0035] In further embodiments, the composition may be formulated as an oral solid, liquid or suspension preparation using suitable excipients.

[0036] In another embodiment, the health care / therapeutic composition of the present invention can be prepared by methods known in the art, including adding suitable excipients together with sucrose isomers to the active ingredient cinnamic acid derivative in a suitable ratio.

[0037] Therefore, the method for preparing the composition of the present invention comprises:

[0038] i. adding 2%-90% w / w of a cinnamic acid derivative to a 10%-90% w / w aqueous solution of a sugar isomer;

[0039] ii. adding 5-90% w / w of a suitable health excipient to the solution of step (i); and iii. stirring the solution of step (ii) to avoid heat-induced sucrose conversion, and then drying to obtain the desired composition.

[0040] In yet another embodiment, the present invention provides a method for enhancing brain function, reducing anxiety, improving learning ability and concentration without anxiety in an individual, the method comprising treating the individual with a health-care effective amount of a composition comprising cinnamic acid or a derivative thereof and a sucrose isomer.

[0041] In yet another embodiment, the present invention provides a method of treating inflammation in a subject, the method comprising treating the subject with a therapeutically effective amount of a composition comprising cinnamic acid or a derivative thereof and a sucrose isomer, wherein the inflammation is selected from inflammation associated with COX 2.

[0042] The term "health-effective amount" refers to an amount that provides the desired nutritional and therapeutic benefit or result to alleviate or reduce or control the progression of a disease.

[0043] The following examples further explain the present invention through experimental conditions. These examples are for illustration only and are not intended to limit the scope of the present invention. Example:

[0044] Illustrative recipe:

[0045] The formulations listed below are for illustrative purposes only and should not be used in any way to limit the proper interpretation of the claims. The percentage of health-care excipients in the formulations varies from 5% to 90%.

[0046] An illustrative recipe is as follows:

[0047] Example 1: Formulation of cinnamic acid derivatives with monosaccharides and disaccharides

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[0050]

[0051] Example 2: Formulation of cinnamate derivatives with monosaccharides and disaccharides

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[0056] Example 3: Formulation of cinnamic acid amide derivatives with monosaccharides and disaccharides

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[0059]

[0060] Example 4: General method for preparing formulations of cinnamic acid derivatives and sucrose isomers

[0061] Cinnamic acid / ester / amide (2-90% w / w) is added to an aqueous solution of D-allose, D-psicose and D-tagatose, L-arabinose, trehalulose, turanose, leucrose and isomaltulose (90-10% w / w), followed by a suitable health care excipient (5-90% w / w). The composition is stirred at room temperature for 1.0-2.0 hours to avoid heat-induced sucrose conversion. The resulting solution / suspension is packaged for use.

[0062] Example 4a:

[0063] 25 g of trehalulose was added to 100 mL of purified water under stirring at room temperature. 0.1 g of n-cocoyl coumarate was slowly added and stirred for 30 minutes, and then 5 g of calcium stearate was added. The resulting solution was stirred at room temperature for 1 hour and dried.

[0064] Embodiment 4b:

[0065] 25 g of isomaltulose was added to 100 mL of purified water under stirring at room temperature. 0.5 g of n-octadecyl ferulate was slowly added, stirred for 30 minutes, and then 5 g of calcium stearate was added. The resulting solution was stirred at room temperature for 1 hour and evaporated to dryness.

[0066] Example 4c:

[0067] 25 g of D-psicose was added to 100 mL of purified water under stirring at room temperature. 1 g of n-trans-caffeoyl-tyramine 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 freeze-dried.

Claims

1. A composition comprising cinnamic acid derivatives and sucrose / sugar isomers having nutritional / therapeutic value, in, The content of cinnamic acid derivatives is 2%-90% w / w, and the content of sucrose / sugar isomers is 10%-90% w / w.

2. The composition according to claim 1, wherein the composition comprises 5-90% of a health / therapeutic excipient.

3. The composition according to claim 1, wherein the cinnamic acid derivative is selected from hydroxycinnamic acid, esters and amides thereof.

4. The composition according to claim 3, wherein the 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 composition according to claim 3, wherein the cinnamate derivative is selected from alkyl / aralkyl alcohols esterified with cinnamic acid, and has the general formula CA-CO-OR, wherein CA represents cinnamic acid, R represents a C1-C22 alkyl chain, Ph-CH 2 CH 2 - or CA-CO-O(CH)nO-CO-CA; n = 1-10, wherein the cinnamate includes a branched alkyl group, such as isopropyl, isobutyl cinnamate, isopentyl, etc.

6. The composition according to claim 3, wherein the cinnamic acid amide derivative is selected from amides having the general formula CA-CO-NHR, wherein CA represents cinnamic acid and NHR represents tyramine, 5-hydroxytryptamine, dopamine, phenylethylamine.

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

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

9. The composition according to claim 7, wherein the isomers of the disaccharide are selected from trehalose, turanose, leucrose and isomaltulose.

10. The composition of claim 2, wherein the composition may contain a health / therapeutic excipient selected from binders, diluents, lubricants, stabilizers, solubilizers, sustained release polymers, colorants, flavor enhancers, and the like.

11. The composition of any one of claims 1 to 10, wherein the composition can be formulated as an oral solid, liquid or suspension.

12. The composition comprising a cinnamic acid derivative and a sucrose isomer as claimed in any one of claims 1 to 11 as a health care / therapeutic composition.

13. A method for preparing a composition, include: i. adding 2%-90% w / w of a cinnamic acid derivative to a 10%-90% w / w aqueous solution of a sugar isomer; ii. adding 5-90% w / w of a suitable health excipient to the solution of step (i); and iii. The solution of step (ii) is stirred to avoid heat-induced sucrose conversion and then dried to obtain the desired composition.

14. A method of enhancing brain function, reducing anxiety, improving learning ability and concentration without anxiety in an individual, wherein the method comprises providing the individual with a health-care effective amount of the composition comprising cinnamic acid or a derivative thereof and a sucrose isomer as claimed in any one of the preceding claims.

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

16. A composition comprising a cinnamic acid derivative and a sucrose isomer as claimed in any one of the preceding claims for use in enhancing brain function, reducing anxiety, improving learning ability and concentration without anxiety.

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

18. A composition comprising a cinnamic acid derivative and a sucrose isomer as claimed in any one of the preceding claims for use as an intelligence enhancer and for pain management.

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