Field of the invention

The present invention relates, generally, to the field of the composition containing mulberry extract (Morns alba or Morus spp.) which the said composition can be used as tonic and/or adaptogenic agent; cognitive enhancer and reducing risks of liver diseases, peptic ulcers, metabolic syndromes, obesity and/or cardiovascular diseases.

Background of the invention

Morus spp., kno n as mulberry, is a fast-growing small to medium-sized plant. The leaves are alternately arranged, simle and often lobed and serrated on the margin. The taxonomy of Morus is complex with more than 150 published species names including Morus alba L., Morus australis Poir, Morus cathayana, Morus celtidifolia Kunth, Morus indica - L., Morus insignis, Morus japonica Audib, Morus liboensis S.S., Morus macroura, Morus mesozygia Stapf, Morus mongolica, Morus nigra L., Morus notabilis C.K. Schneid., Morus rubra L, Morus serrata, Roxb., Morus trilobata, Morus wittiorum Hand.-Mazz.

The mulberry fruits are multiple fruit, approximately 2-3 cm long. Immature fruits are usually white, green or pale yellow. In most species the fruits turn pink and then red while ripening, then dark purple or black. However, the fruits of the white-fruited cultivar are white when ripe. Mulberry fruit color derives from anthocyanins which is water-soluble. Normally, anthocyanin content depends on climate and area of cultiva ion, and is especially high in tropical area. The ripe fruits are edible and commonly consumed as fruit or juice. Leaves are also edible in the form of tea.

The uses of Morus spp. or mulberry extract are mostly in the field of cosmetics. Only a few reports have been found that the Morus spp. or mulberry extract are used as nutraceutical or functional ingredients or foods such as a composition comprising the crude extract of the fruit of Morus alba L having neuro-protective activity (WO 2004/006946 Al) or an edible products with thermostatic and cognitive effects (US 2012/0087997 Al) which indicates that the said edible products comprising a mulberry extract. The prior inventions also includes the use of mulberry extract as an active ingredient in anorectic agent and air regulator for diet (US 2006/0222720 Al) and the use of mulberry extract as an ingredient in nutritional composition and method for increasing creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and for aiding recovery following exercise (US 2007/0196508 Al) and the use of mulberry extract together with other medicinal plant extracts in chewing gum, confection, and other oral delivery vehicles containing a traditional Chinese medicine or extract thereof (US 2010/0104518 Al).

This invention is aimed to improve health benefit of the mulberry extract by combined with some additional compounds wherein the combination provides increasing efficiency of said compounds in terms of cognitive enhancing effect and reduces risks of liver diseases, peptic ulcers, metabolic syndromes, obesity and/or cardiovascular diseases.

Summary of the invention

A composition containing mulberry juice or concentrate or mulberry powder or extract wherein the said mulberry is obtained from mulberry leaves or fruits. The composition according to this invention is obtained from the process either not using organic solvents or extracted with water and alcohol wherein the said extract comprises of phenolic or flavonoid compounds including anthocyanins, gallic acid, rutin or combination thereof. The composition according to this invention can be used as tonic and/or adaptogenic agent; cognitive enhancer and reducing the risks of liver diseases, peptic ulcers, metabolic syndromes, obesity and/or cardiovascular diseases. The uses of the composition according to this invention can be in food, beverage, food supplement or health products in any forms.

Brief description of the drawing

1. Figure 1 illustrates that the light microscope of liver tissue sections was stained with hematoxylin and eosin (H&E) at 20X magnification. A: Normal diet (ND) + vehicle, B: HCHF + vehicle, C: OVX-HCHF diet + vehicle, D: OVX-HCHF diet + Isoflavone 15 mg/kg B W, E: OVX-HCHF diet + L-camitine 250 mg/kg B W, F: OVX-HCHF diet + MME 10 mg/kg BW, G: OVX-HCHF diet + MME 50 mg/kg BW and H: OVX-HCHF diet + MME 250 mg/kg BW. ND: normal diet, HCHF: high carbohydrate high fat diet, Veh: vehicle, OVX-HCHF: ovariectomized plus high carbohydrate high fat diet, Iso: the isoflavone at dose of 15 mg/kg BW, MME10, 50 and 250: the microencapsulated mulberry fruits extract at dose of 10, 50 and 250 mg/kg BW, respectively. Figure 2 illustrates that the effect of various doses of MME on the relative density of NF- kB and TNF-a in liver tissue was detected by Western blotting (a) and quantitatively analyzed (b). The levels of b-actin were normalized against the level of NF-kB and TNF- α. Their relative density of NF-kB and TNF-a levels were calculated against those of control normal diet plus vehicle rats. Data are presented as mean ± SEM (n=6/group). ^{a,aa, aaa} p-value<.05, .01, .001 respectively; compared to control rats which received normal diet and vehicle and *, ** p-value<.05, .01 respectively; compared to OVX rats which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, Veh: vehicle, OVX-HCHF: ovariectomized plus high carbohydrate high fat diet, Iso: the isoflavone at dose of 15 mg/kg BW, MME 10, 50 and 250: the microencapsulated mulberry fruits extract at dose of 10, 50 and 250 mg/kg BW, respectively. Figure 3 illustrates that the effect of various doses of MME on the relative density of DNMT-1 and PPAR-γ in liver tissue was detected by Western blotting (a) and quantitatively analyzed (b). The levels of b-actin were normalized against the level of DNMT-1 and PPAR-γ. Their relative density of DNMT-1 and PPAR-γ levels were calculated against those of control normal diet plus vehicle rats. Data are presented as mean ± SEM (n=6/group). ^{a, aaa} p-value<.05, .001 respectively; compared to control rats which received normal diet and vehicle, ^b p-value<.05; compared to normal rats which received HCHF diet and vehicle and *, *** p-value<.05, .001 respectively; compared to OVX rats which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, Veh: vehicle, OVX-HCHF, ovariectomized which received high carbohydrate high fat diet, Iso: the isoflavone at dose of 15 mg. kg ^"1 BW, L-car: the L-camitine at dose of 250 mg. kg ^'1 BW, MME 10, 50 and 250: the microencapsulated mulberry fruits extract at dose of 10, 50 and 250 mg. kg ^"1 BW, respectively. Figure 4 illustrates the effect of mulberry fruits on gastric inflammation of rats orally treated with vehicle or ranitidine 50 mg/kg BW or mulberry fruits 2, 10, 50 mg/kg BW. Data were prese ted as mean ± SEM (n=5/group). ^aaa P -value < 0.001 compared with control treated group ^* P-value < 0.05 compared with vehicle treated group ^** P-value < 0.01 compared with vehicle treated group ^*** P-value < 0.001 compared with vehicle treated group. Figure 5 illustrates a photograph of the effect of mulberry fruits on gastric inflammation of rats orally treated with vehicle or ranitidine or mulberry fruits powder. (A: Control (Naive intact), B: Vehicle + stress, C: Mulberry fruits 2 mg/kg BW + stress, D: Mulberry fruits 10 mg/kg B W + stress, E: Mulberry fruits 50 mg/kg BW + stress, F : Ranitidine 50 mg/kg BW + stress). Figure 6 illustrates that the effect of various doses of MME on the relative density of NF- kB and TNF-a in adipose tissue was detected by Western blotting (a) and quantitatively analyzed (b). The levels of b-actin were normalized against the level of NF-kB and TNF- α. Their relative density of NF-kB and TNF-a levels were calculated against those of control normal diet plus vehicle rats. Data are presented as mean ± SEM (n=6/group). ^{a, aa, aaa} p-value<.05, .01, .001, respectively; compared to control rats, which received normal diet and vehicle, ^b p-value<.05; compared to normal rats, which received HCHF diet and vehicle and **, *** p-value<.01, .001, respectively; compared to OVX rats, which received HCHF and vehicle. ND: normal diet, HCHF : high carbohydrate high fat diet, Veh: vehicle, OVX-HCHF: ovariectomized plus high carbohydrate high fat diet, Iso: the isoflavone at dose of 15 mg/kg BW, L-car: the L-camitine at dose of 250 mg/kg BW, MME10, 50 and 250: the microencapsulated mulberry fruits extract at dose of 10, 50 and 250 mg/kg BW, respectively. Figure 7 illustrates that the effect of various doses of MME on the relative density of PPAR-γ in adipose tissue was detected by Western blotting (a) and quantitatively analyzed (b). The levels of b-actin were normalized against the level of PPAR-γ. Their relative density of PPAR-γ levels were calculated against those of control normal diet plus vehicle rats. Data are presented as mean ± SEM (n=6/group). ^a p-value<.05; compared to control rats, which received normal diet and vehicle and **, *** p-value<.01, .001, respectively; compared to OVX rats, which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, Veh: vehicle, OVX-HCHF: ovariectomized plus high carbohydrate high fat diet, Iso: the isoflavone at dose of 15 mg/kg BW, L-car: the L- c ami tine at dose of 250 mg/kg BW, MME 10, 50 and 250: the microencapsulated mulberry fmits extract at dose of 10, 50 and 250 mg/kg BW, respectively. Figure 8 illustrates that the light microscope of white adipose tissue at gonadal area were stained with hematoxylin and eosin (H&E) at 40X magnification. A: Normal diet (ND) + vehicle, B: HCHF + vehicle, C: OVX-HCHF diet + vehicle, D: OVX-HCHF diet + Isoflavone 15 mg/kg BW, E: OVX-HCHF diet + L-camitine 250 mg/kg BW, F: OVX- HCHF diet + MME 10 mg/kg BW, G: OVX-HCHF diet + MME 50 mg/kg BW and H: OVX-HCHF diet + MME 250 mg/kg BW. . Figure 9 illustrates that the light microscope of white adipose tissue at mesenteric area were stained with hematoxylin and eosin (H&E) at 40X magnification. A: Normal diet (ND) + vehicle, B: HCHF + vehicle, C: OVX-HCHF diet + vehicle, D: OVX-HCHF diet + Isoflavone 15 mg/kg BW, E: OVX-HCHF diet + L-camitine 250 mg/kg BW, F: OVX- HCHF diet + MME 10 mg/kg BW, G: OVX-HCHF diet + MME 50 mg/kg BW and H: OVX-HCHF diet + MME 250 mg/kg BW.

10. Figure 10 illustrates that the light microscope of white adipose tissue at retroperitoneal area were stained with hematoxylin and eosin (H&E) at 40X magnification. A: Normal diet (ND) + vehicle, B: HCHF + vehicle, C: OVX-HCHF diet + vehicle, D: OVX-HCHF diet + Isoflavone 15 mg/kg BW, E: OVX-HCHF diet + L-camitine 250 mg/kg BW, F: OVX- HCHF diet + MME 10 mg/kg BW, G: OVX-HCHF diet + MME 50 mg/kg BW and H: OVX-HCHF diet + MME 250 mg/kg BW.

11. Figure 11 illustrates that the light microscope of white adipose tissue at subcutaneous area were stained with hematoxylin and eosin (H&E) at 40X magnification. A: Normal diet (ND) + vehicle, B: HCHF + vehicle, C: OVX-HCHF diet + vehicle, D: OVX-HCHF diet + Isoflavone 15 mg/kg BW, E: OVX-HCHF diet + L-camitine 250 mg/kg BW, F: OVX- HCHF diet + MME 10 mg/kg BW, G: OVX-HCHF diet + MME 50 mg/kg BW and H: OVX-HCHF diet + MME 250 mg/kg BW.

12. Figure 12 illustrates the effect of various doses of MME on density of adipocytes at all regions. Data are presented as mean ± SEM (n=6/group). ^aa ’ ^aaa p-value<.01, .001, respectively; compared to control rats, which received normal diet and vehicle, ^{bb, bbb} p- value<.01, .001, respectively; compared to normal rats, which received HCHF diet and vehicle and *, **, *** p-value<.05, .01, .001, respectively; compared to OVX rats, which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, Veh: vehicle, OVX-HCHF: ovariectomized plus high carbohydrate high fat diet, Iso: the isoflavone at dose of 15 mg/kg BW, L-car: the L-camitine at dose of 250 mg/kg BW, MME10, 50 and 250: the microencapsulated mulberry fruits extract at dose of 10, 50 and 250 mg/kg BW, respectively.

13. F igure 13 illustrates the effect of various doses of MME on size of adipocytes at all regions. Data are presented as mean ± SEM (n=6/group). ^aaa p-value<.001 ; compared to control rats, which received normal diet and vehicle and *, **, *** p-value<.05, .01, .001, respectively; compared to OVX rats, which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, Veh: vehicle, OVX-HCHF: ovariectomized plus high carbohydrate high fat diet, Iso: the isoflavone at dose of 15 mg/kg BW, L-car: the L- camitine at dose of 250 mg/kg BW, MME10, 50 and 250: the microencapsulated mulberry fruits extract at dose of 10, 50 and 250 mg/kg BW, respectively.

Detailed description of the invention

A composition containing mulberry extract comprises of at least a mulberry extract, a sweetener, and an additive wherein each composition contains the following amount:

Mulberry extract 1 -60% w/w

Sweetener 0.9-60% w/w

Additive making 100% w/w of total amount wherein the additive can be chosen from Maltodextrin, bulking agent, stabilizing agent, anticaking agent, acidulant, gelling agent, artificial flavor, food coloring, water, and milk.

One or more embodiment of the present invention will be described in detail with reference to a sample composition containing mulberry extract. However, a sample composition containing mulberry extract according to the present invention is not intended to limit the scope of one or more embodiment of the present invention. The following examples are provided to show one certain embodiment of the invention. It will be understood by those skilled in the art that the present invention is not limited by the specific embodiment of the following examples:

1) A composition containing mulberry extract in the form of capsule comprises of a. Mulberry extract 1 -60% w/w b. Maltodextrin 19-60% w/w c. Stabilizing agent which can be chosen from Gum Arabic or Polydextrose 2-20% w/w The composition containing mulberry extract in the form of capsule also comprises of bulking agent which can be chosen fr m cassava flour or lactose of 0.01-37% w/w or anticaking agent which can be chosen from magnesium stearate or silicon dioxide of 0.01-37% w/w.

2) A composition containing mulberry extract in the form of instant powder drink comprises of a. Mulberry extract 1-60% w/w b. Bulking agent 36-98% w/w c. Sweetener 0.9-3% w/w d. Acidulant 0.1-1% w/w

3) A composition containing mulberry extract in the form of gel drink comprises of a. Mulberry extract 1 -60% w/w b. Water 38-84% w/w c. Sweetener 0.9-12% w/w d. Gelling agent 1 -2% w/w e. Acidulant 0.1-1% w/w

4) A composition containing mulberry extract and milk in the form of powdered milk drink comprises of a. Mulberry extract 2-50% w/w b. Milk 47-97% w/w c. Sweetener 1-3% w/w

5) A composition containing mulberry extract and milk in the form of milky drink comprises of a. Mulberry extract 1-50% w/w b. Milk 20-87% w/w c. Sweetener 1 -6% w/w d. Maltodextrin 7-10% w/w e. Carrageenan 1-10% w/w with an addition of artificial flavor and/or food coloring.

A composition containing mulberry extract according to the present invention wherein the mulberry extract is obtained fr m essential substance of either mulberry fruits or leaves or combination thereof by a solvent which is preferably an organic solvent which can be chosen from either water or alcohol or combination thereof or it is obtained without using a solvent, e.g. supercritical fluid extraction which uses substance in a condition hen temperature and pressure are above a critical point, or microwave-assisted extraction, or ultrasonic extraction.

One or more embodiment of the present invention will be described in detail with reference to a sample composition containing mulberry extract. However, a sample composition containing mulberry extract according to the present invention is not intended to limit the scope of one or more embodiment of the present invention. The following examples are provided to show one certain embodiment of the invention. It will be understood by those skilled in the art that the present invention is not limited by the specific embodiment of the following examples:

1) Drying

Bake mulberry fruits at temperature of 50-60 degree Celsius for 48-72 hours or until moisture is less than 10% and then grind it into powder.

2) Extraction of mulberry extract

Perform an extraction of dried mulberry powder by a solvent, i.e. water or alcohol, by soaking mulberry powder in a solvent for 1-3 days and stir it every 6 hours repeatedly for 2-3 rounds. Then, filter out and take filtered water for drying by a spray dryer or freeze dryer and then the extract can be mixed with several products.

This invention discloses the composition containing mulberry juice or concentrate or mulberry powder or extract wherein the said mulberry is obtained from mulberry leaves or fruits. The mulberry leaves or fruits according to this invention can be derived from Morns alba L., Morus australis Poir, Morus cathayana, Morus celtidifolia Kunth, Morus indica - L., Morus insignis , Morus japonica Audib, Morus liboensis S.S. , Morus macroura, Morus mesozygia Stapf , Morus mongolica, Morus nigra L. , Morus notabilis C.K. Schneid., Morus rubra L, Morus s errata, Roxb. , Morus triloba ta, Morus wittiorum Hand.-Mazz.

The mulberry extract according to this invention comprises of phenolic or flavonoid compounds comprise of anthocyanins, gallic acid, rutin as sho n in Table 1.

Table 1 Phenolic compositions of mulberry fruits

The phenolic compounds and flavonoids content in the mulberry extract according to this invention is ranging from 0.1 to 1000 microgram GAE/g extract and the anthocyanins content is ranging from 100-1000 microgram/g extract.

The composition containing the mulberry extract according to this invention can be used as tonic and/or adaptogenic agent, cognitive enhancer and reducing the risks of liver diseases, peptic ulcers, metabolic syndromes, obesity and/or cardiovascular diseases. The adaptogenicity property of the composition containing the mulberry extract according to this invention is caused by exerting the effect at multi-target organs including but not limited to the modifications of sympathetic effects, oxidative stress balances as shown in Tables 2 and 3. Table 2 The effect of various doses of MME on the activities of acetylcholine esterase (AChE) and monoamine oxidase (MAO) in hippocampus Data are presented as mean ± SEM (n=6/group). ^aaa p-value<.001 respectively; compared to normal rats which received normal diet, ^bbb p-value<.001; compared to normal rats which received HCHF diet and vehicle and vehicle and *, **, *** p-value<.05, .01, .001 respectively; compared to OVX rats which received HCHF and vehicle. ND, normal diet; HCHF, high carbohydrate high fat diet; OVX-HCHF, ovariectomized plus high.

Table 3 The effect of various doses of MME on the activities of acetylcholine esterase (AChE) and monoamine oxidase (MAO) in prefrontal cortex

Data are presented as mean ± SEM (n=6/group). ^ ^aaa p-value<.01, .001 respectively; compared to normal rats w ich received normal diet and vehicle and *, **, *** p-value<.05, .01, .001 respectively; compared to OVX rats which received HCHF and vehicle. ND, normal diet;

HCHF, high carbohydrate high fat diet; OVX-HCHF, ovariectomized plus high carbohydrate high fat diet; MME10, 50 and 250, the microencapsulated mulberry fruits extract at dose of 10, 50 and 250 mg/kg BW.

It is known that when proinflammatory cytokines i.e. NF-kB, TNF-alpha is suppressed or the functions of peroxisome proliferating activated receptors and epigenetic mechanisms are modified, the risks of liver disease can be reduced. Therefore, the composition containing the mulberry extract according to this invention can be used for preventing or reducing the risk of liver disease due to its biological activities as shown in Tables 4-6 and figure 1. Table 4 Serum biochemical parameters

Data are presented as mean ± SEM (n=6/group). ^a ’ ^aa p-value<05, .01 respectively; compared to control rats which received normal diet and vehicle, ^bb p-value<01; compared to normal rats which received HCHF diet and vehicle and *, **, *** p-value<05, .01, .001 respectively; compared to OVX rats which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, OVX+HCHF: ovariectomized rats which received high carbohydrate high fat diet, MME10, 50 and 250: the microencapsulated mulberry fruits extract at doses of 10, 50 and 250 mg/kg BW.

Table 5 The effect of various doses of MME on oxidative stress status in liver

Data are presented as mean ± SEM (n=6/group). ^a · ^aaa p-value<05, .001 respectively; compared to control rats which received normal diet and vehicle, and *, **, *** p-value<05, .01, .001 respectively; compared to OVX rats which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, OVX+HCHF: ovariectomized rats which received high carbohydrate high fat diet, MME10, 50 and 250: the microencapsulated mulberry fruits extract at doses of 10, 50 and 250 mg/kg BW.

Table 6 The effect of various doses of MME on liver histopathology

Data are presented as mean ± SEM (n=6/group). ^{a, aa, aaa} p-value<.05, .01 , .001 respectively; compared to control rats which received normal diet and vehicle, ^{b, bb, bbb} p-value<.05, .01, .001 respectively; compared to normal rats which received HCHF diet and vehicle and *, **, *** p- value<.05, .01, .001 respectively; compared to OVX rats which received HCHF and vehicle. ND: normal diet, HCHF: high carbohydrate high fat diet, OVX+HCHF: ovariectomized rats which received high carbohydrate high fat diet, MME10, 50 and 250: the microencapsulated mulberry fruits extract at doses of 10, 50 and 250 mg/kg BW.

The potential use of the composition according to this invention for reducing risk of peptic ulcers by decreasing oxidative stress by the mulberry extract as shown in Figures 4 and 5 and Table 7.

Table 7 The effect of mulberry fruits on malondialdehyde (MDA) level and oxidative stress in hippocampus of rats exposed to cold immobilization stress

MF: Mulberry fruit T: tianeptine

The potential use of the composition according to this invention for reducing risk of metabolic syndrome by reducing of adipocytes, improving metabolic profiles, decreasing adiposity index, decreasing oxidative stress and suppressing proinflammatory cytokines i.e. NF- kB, TNF-alpha and/or modifying the functions of peroxisome proliferating activated receptors and suppressing pancreatic lipases by the mulberry extract as shown in Tables 8-9.

Table 8 The effects of microencapsula ed mulberry fruits extract (MME) on metabolic parameters

Data are presented as meani SEM (n=6/group). ^{a, aa, aaa} p-value<.05, .01, .001, respectively; compared to control rats, which received normal diet and vehicle, ^{b, bb,bbb} p-value<.05, .01, .001, respectively; compared to normal rats, which received HCHF diet and vehicle and *, **, *** p- value<05, .01, .001, respectively; compared to OVX rats, which received HCHF and vehicle. Table 9 The effect of various doses of MME on oxidative stress markers in adipose tissue

Data are presented as mean ± SEM (n=6/group). ^{a, aa, aaa} p-value<.05, .01, .001, respectively; compared to control rats, which received normal diet and vehicle, ^bb p-value<.01; compared to normal rats, which received HCHF diet and vehicle and *, **, *** p-value< .05, .01 , .001, respectively; compared to OVX rats, which received HCHF and vehicle. The potential use of the composition according to this invention for reducing risk of obesity by reducing of adipocytes, improving metabolic profiles and decreasing adiposity index caused the mulberry extract as shown in Figures 8 to 13.

The potential use of the composition according to this invention for reducing risk of cardiovascular diseases by suppressing angiotensin converting enzymes and/or improving Atherogenic index caused by the mulberry extract as shown in Table 10.

Table 10 The effects of microencapsulated mulberry fruits extract (MME) on angiotensin converting enzymes (ACE) and Atherogenic index (AI) Data are presented as mean ± SEM (n=6/group). ^{a> aa> aaa} p-value<05, .01 , .001 , respectively; compared to control rats, which received normal diet and vehicle, ^{b, bb, bbb} p-value<.05, .01, .001, respectively; compared to normal rats, which received HCHF diet and vehicle and *, **, *** p- value<05, .01, .001, respectively; comparedto OVX rats, which received HCHF and vehicle. The composition containing the mulberry extract according to this invention can be used for improving cognitive functions by enhancing cholinergic functions and/or decreasing oxidative stress status and/or neurogenesis and/or enhancing signal transduction via mitogen activated protein kinase (MAPK) in a brain as shown in Table 11.

Table 11 The effect of various doses of MME on oxidative stress markers in hippocampus Data are presented as mean ± SEM (n=6/group). ^a,aa,aaa p-value<.05, .01, .001 respectively; compared to control rats which received normal diet and vehicle, ^bbb p-value<001; compared to normal rats which received HCHF diet and vehicle and *, **, *** p-value<05, .01, .001 respectively; compared to OVX rats which received HCHF and vehicle.

The composition according to this invention can be used in food, food products, beverages, milk or food supplement or health products wherein the food, beverage, milk or food supplement or health products can be in the form of tablet, capsule, effervescent granule or tablet, granule, powder, gel, jelly, gum, candy, spray, film, patch, cream, ointment, lotion or similar.