JP6811520B2 - Protease activity promoting material - Google Patents

Description

The present invention relates to compositions and agents that promote protease activity.

Protease is a general term for enzymes that catalyze the hydrolysis of peptide bonds in proteins and peptides. Proteases are roughly classified into two types according to their catalytic action. Endoproteses (proteinases) catalyze the release of peptides by hydrolyzing peptide bonds inside molecules such as proteins and peptides, and these molecules An exoprotease catalyzes the release of an amino acid by hydrolyzing a peptide bond from the amino group terminal or the carboxyl group terminal.

Proteases play a major role in the homeostasis of living organisms, such as nutrient absorption by degrading food proteins and peptides in the living body, decomposition of unnecessary proteins, and regulation of protein activity.

In vitro, protease also plays an important role in relation to skin aging symptoms. The stratum corneum of the epidermis in the skin is located in the outermost layer of the living body and has a function of protecting the living body from external stimuli. The epidermal cells divided in the basal layer are sequentially pushed up to the outer layer while changing their morphology, and finally desorbed to repeat metabolism. However, due to environmental stress such as aging and ultraviolet rays, and increased keratinization due to inflammation, the metabolic cycle of epidermal cells is disturbed, causing spots and dullness, wrinkles / fine wrinkles, and rough skin to disappear. There may be aging symptoms such as things. Epidermal cells are bound to each other by proteins called desmosomes and desquamate by the action of proteases present in the stratum corneum of the epidermis. Proteases promote the metabolism of epidermal cells by degrading desmosomes and suppress skin aging symptoms.

As described above, a protease activity promoter containing cornflower, gajumaru, raspberry, grapefruit, cornflower, hawthorn, jujube and paracress as an active ingredient as an active ingredient for promoting the activity of proteases that play important roles in and out of the living body. Is known (see Patent Document 1).

Japanese Unexamined Patent Publication No. 2008-081441

However, the protease activity-promoting agent described in Patent Document 1 does not have a sufficient protease activity-promoting action. In particular, the protease activity-promoting agent described in Patent Document 1 requires a very high concentration of the active ingredient with respect to the protease whose activity should be promoted.

Therefore, the present invention is a problem to be solved by the present invention to provide a composition and an agent containing a natural product-derived ingredient as an active ingredient, which can promote the activity of protease at a relatively low concentration. To do.

As a result of intensive research on the above-mentioned problems and investigation of the activity promoting activity of proteases for various substances, the present inventors surprisingly found that when a low concentration of camcam berry was combined with papaya, it was significantly more remarkable than papaya alone. It was found that a protease activity-promoting effect was observed in Papaya. Then, they succeeded in creating a composition and an agent containing papaya and camu camu berry as a protease activity promoting composition and a protease activity promoting agent. The present invention is an invention completed based on such findings and successful examples.

Therefore, according to the present invention, a cosmetic composition containing papaya and camu camu berry is provided.

According to another aspect of the present invention, a protease activity promoting composition containing papaya and camu camu berry is provided.

According to another aspect of the present invention, a protease activity promoter containing papaya and camu camu berry is provided.

According to the present invention, since it contains papaya and camu camu berry, it is possible to promote the activity of protease at a relatively low concentration.

FIG. 1 is a diagram showing the results of measuring the protein digestibility of the combination of the papaya extract and the camu camu berry fruit powder described in the examples. The graph shows the mean value and the bar shows the standard deviation (n = 3).

The details of the present invention will be described below.
The present invention is a cosmetic composition, a protease activity promoting composition, and a protease activity promoting agent, which exhibit a protease activity promoting action by containing papaya and camu camu berry as active ingredients. In the present specification, the present invention is collectively referred to as "the composition and agent of the present invention".

Papaya is not particularly limited as long as it is a papaya genus plant known as a fruit native to tropical America, and examples thereof include Carica papaya . The camu camu berry is not particularly limited as long as it is a berry-based Myrtaceae plant native to the tropical rainforests of South America, and examples thereof include Myrciaria dubia . For papaya and camu camu berry, any part may be used, but the part excluding the seed is preferably used, and the pericarp and the flesh part (hereinafter, simply referred to as the fruit part) which is the part excluding the seed of the fruit. ) Is more preferably used.

Papaya and camu camu berries are preferably those immediately after harvest or those processed immediately after harvest. If it takes time to process, it is preferable to store the papaya and camu camu berries by a storage means usually used by those skilled in the art such as low temperature storage in order to prevent deterioration.

Papaya and camu camu berries may be these processed products. Processed products of papaya and camu camu berry include, for example, dry powder of papaya and camu camu berry, shreds of papaya and camu camu berry and their dry powder, squeezed juice of papaya and camu camu berry and their dry powder, papaya and camu camu berry. Examples include, but are not limited to, extracts and dry powders thereof. However, from the viewpoint of ease of processing, storage, transportation, etc. and versatility of the usage form, it is preferable that the final form is a dry powder. For example, for camu camu berry, a dry powder of the fruit part of camu camu berry is preferable, and for papaya, a papaya extract and a dry powder thereof are preferable.

For example, conventionally known methods can be used to dry and powder papaya and camu camu berries. As such a method, a method in which a drying treatment and a crushing treatment are combined with papaya and camu camu berries can be used. Either the drying treatment or the pulverization treatment may be performed first, but it is preferable to perform the drying treatment first. The dry powdering may be combined with this method, if necessary, with one or more treatments selected from treatments such as sterilization treatments. Further, the number of times of the pulverization treatment may be a combination of one or two or more treatments, but it is preferable to combine a fine pulverization treatment for finer pulverization after the coarse pulverization treatment.

The sterilization treatment is not particularly limited as long as it is a treatment generally known to those skilled in the art, but for example, it is a treatment that physically or chemically kills microorganisms using temperature, pressure, electromagnetic waves, chemicals, or the like. it can. When the sterilization treatment is performed in addition to the drying treatment and the crushing treatment, the sterilizing treatment is preferably performed after the drying treatment or before or after the crushing treatment.

The drying treatment is not particularly limited, and examples thereof include a treatment in which the papaya and camu camu berry are dried so that the water content is 10% or less, preferably 5% or less. The drying treatment can be performed by any method known to those skilled in the art, such as hot air drying, high pressure steam drying, electromagnetic wave drying, and freeze drying. Drying by heating can be performed, for example, at a temperature and time at which the papaya and camu camu berries are not discolored by heating at 40 ° C. to 140 ° C., preferably 80 ° C. to 130 ° C.

The crushing treatment is not particularly limited, and examples thereof include a treatment of crushing a plant by an arbitrary method usually used by those skilled in the art using a crushing device or instrument such as a crusher, a mill, a blender, or a stone mill. The crushed papaya and camu camu berries are screened as needed, and it is preferable to use, for example, those that pass through 30 to 250 mesh as the papaya and camu camu berry powder. By setting the particle size to 250 mesh or less, the papaya and cam camberry powder can be easily handled during further processing, and by setting the particle size to 30 mesh or more, the papaya and cam cam berry powder and others can be handled easily. It facilitates uniform mixing with the material of.

Specific examples of the dry powdering method include a method in which papaya and camu camu berries are cut, dried so as to have a water content of 10% by mass or less, preferably 5% by mass or less, and then pulverized. .. In addition to this, for example, a method in which papaya and camu camu berries are cut, kneaded, then dried and crushed; papaya and camu camu berries are dried, roughly crushed, then heated at 110 ° C. or higher, and further finely divided. Examples include a method of crushing.

The method for shredding papaya and camu camu berry is not particularly limited, but for example, a method usually used by those skilled in the art for shredding plants such as slicing, crushing, and shredding can be used. As an example of fragmentation, it may be made into a slurry. Slurry is performed by mixing papaya and cam cam berries in a mixer, juicer, blender, mascoroider, etc. to make papaya and cam cam berries into a thick porridge (suspension of liquid and solid).

The method for squeezing papaya and camu camu berry is not particularly limited, and examples thereof include a method for squeezing papaya and camu camu berry or its fragment, a method for centrifuging or filtering papaya and camu camu berry fragment. it can. As an example of a specific juice squeezing method, juice is squeezed by a mechanical crushing means such as a mixer or a juicer, and if necessary, a squeezed liquid is obtained by removing crude solids by means such as sieving and filtration. The method can be mentioned.

The method for obtaining an extract of papaya and camu camu berry is not particularly limited, but for example, an extraction solvent usually used by those skilled in the art such as ethanol, water, and hydrous ethanol is added to papaya and camu camu berry or a fragment thereof. If necessary, a method of stirring or heating for extraction can be mentioned. The extract may be concentrated if necessary. However, the papaya extract preferably contains a papaya-derived enzyme such as papain.

Examples of the extraction solvent used for obtaining the extracts of papaya and camouflage berries include, but are not limited to, water, organic solvents, and hydrous organic solvents (hydrous alcohols such as hydrous ethanol). When water is used as a solvent, hot water or hot water may be used. As the organic solvent used for extraction, an organic solvent usually acceptable for extracting natural components is used, and for example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, etc. Acetone, hexane, cyclohexane, propylene glycol, hydrous ethanol, hydrous propylene glycol, ethylmethylketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible fats and oils, 1,1,1,2-tetrafluoroethane, 1, 1,2-Trichloroethane and the like can be mentioned. These solvents may be used alone or in combination of two or more. Among these solvents, hot water, hydrous ethanol and hydrous propylene glycol are preferably used.

The extraction method of papaya and camu camu berry is not particularly limited as long as it is usually an acceptable method for extracting natural product components, and examples thereof include solid-liquid extraction methods such as a heating extraction method and a supercritical fluid extraction method. Be done.

The heating extraction method is, for example, a method in which a test substance and a solvent are brought into contact with each other and treated at a temperature equal to or lower than the boiling point of the solvent to extract components contained in the test substance into the solvent. It may be a reflux extraction method.

The supercritical fluid extraction method is, for example, a method of extracting using a supercritical fluid which is a fluid in a state where the critical point (critical temperature, critical pressure) of the gas or liquid of a substance is exceeded. Examples of the supercritical fluid include carbon dioxide, ethylene, propane, nitrous oxide (laughing gas) and the like, but carbon dioxide is preferable.

In the supercritical fluid extraction method, an extraction step of extracting the target component with the supercritical fluid and a separation step of separating the target component and the supercritical fluid are performed. In the separation step, any of extraction separation due to pressure change, extraction separation due to temperature change, and extraction separation using an adsorbent / absorbent may be performed.

Supercritical fluid extraction by the entrainer addition method may be performed. In this method, the extraction fluid is, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, and ketones at 2 to 20 W / V. By adding about% and performing supercritical fluid extraction using this fluid, the solubility of the target extract in the extraction solvent is dramatically increased, or the selectivity of separation is enhanced, which is efficient. Extracts of papaya and cam cam berry can be obtained.

Since the supercritical fluid extraction method can be operated at a relatively low temperature, it has the advantage that it can be applied to substances that deteriorate and decompose at high temperatures, the advantage that the extraction fluid does not remain, and the solvent can be recycled, so the solvent is removed. There is an advantage that the process can be omitted and the process is simplified.

In addition to the above-mentioned extraction method, the extraction method of papaya and camu camberry may be carried out by a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method or the like. Moreover, you may combine a plurality of extraction methods. By combining a plurality of extraction methods, it is possible to obtain extracts of papaya and camu camu berries having various compositions.

The papaya and camouflage berry extracts obtained by extraction can be purified by ultrafiltration, column method using adsorptive carrier (Diaion HP-20, Sephadex-LH20, chitin, etc.), batch method, etc. It is preferable from the viewpoint of safety.

In the present invention, commercially available papaya and camu camu berries and processed products of papaya and camu camu berries used as active ingredients may be used, and examples thereof include those described in Examples described later.

By containing papaya and camu camu berries, the compositions and agents of the present invention exhibit an action of promoting protease activity on casein prepared to be fat-free, as demonstrated by Examples described later. The degree of protease activity promoting action in the composition and agent of the present invention is not particularly limited, but for example, the degree of protein digestibility is higher than that of papaya extract alone by measuring the protein digestibility described in Examples described later. The protein digestibility is preferably 55,000 units / g or more, more preferably the protein digestibility is 58,000 units / g or more, still more preferably the protein digestibility is 60,000 units / g or more, and further. It is preferably 62,000 units / g or more.

In addition, the composition and agent of the present invention contain papaya and camcam berry, and through a protease activity promoting action, a nutrient absorption promoter, a proteolytic agent, a protein activity regulator, a skin aging inhibitor, a skin external preparation, etc. Can be taken.

The content of papaya and camu camu berry in the composition and agent of the present invention may consist of only the active ingredient as long as it is at least an effective amount capable of exerting a protease activity promoting action.

The contents of papaya and cam cam berry are not particularly limited, and for example, the mass ratio of papaya extract and cam cam berry fruit powder ([papaya extract]: [cam cam berry fruit powder]) is 1: 0.001 to 1. , It is preferably 1: 0.005 to 0.5, and more preferably 1: 0.01 to 0.2.

The total content of papaya and camu camu berries is set so that the lower limit of the daily usage is the dry mass of papaya and camu camu berries, for example, 5 mg or more, preferably 10 mg or more, more preferably 15 mg or more. can do. Further, the upper limit of the daily usage amount may be set to be, for example, 2,000 mg or less, preferably 1,500 mg or less, and more preferably 1,000 mg or less in terms of the dry mass of papaya and camu camu berry. it can.

Specifically, the content of the active ingredient is 5 to 5,000 mg, preferably 10 to 2,000 mg, based on the dry mass of papaya and camu camu berry as the amount used per day. However, when the composition and the agent of the present invention contain other substances having a protease activity promoting action, the contents of papaya and camu camu berry can be appropriately adjusted accordingly.

In addition to the active ingredient, the compositions and agents of the present invention may contain other ingredients selected as appropriate. Other ingredients include, for example, various excipients, binders, lubricants, stabilizers, diluents, bulking agents, thickeners, emulsifiers, colorants, fragrances, additives, cosmetic raw materials, pharmaceutical raw materials, etc. Can be mentioned. The content of other components can be appropriately selected depending on the usage form of the composition and the agent of the present invention.

The compositions and agents of the present invention can be used in various forms for the purpose of exhibiting a protease activity promoting action, and can be, for example, oral or parenteral forms. The composition and agent of the present invention may be used orally or parenterally as they are, depending on the form thereof, or may be dissolved orally or parenterally in a solvent for dissolving papaya and camu camu berry. May be used as a target.

The form of the composition and the agent of the present invention is not particularly limited and may be any form. Examples of the forms of the composition and the agent for oral use include forms suitable for oral use, specifically, granules, powders, tablets, chewables, capsules, liquids, syrups and the like. Be done.

The forms of the composition and agent for parenteral use include, for example, a form suitable for parenteral use, specifically, a lotion, a cream, a liquid, a foundation, a mist, an emulsion, and a spray. , Mousse-like, gel-like, etc.

The packaging form of the composition and the agent of the present invention is not particularly limited and may be appropriately selected depending on the dosage form and the like. For example, a blister pack such as PTP; strip packaging; heat seal; aluminum pouch; plastic or synthetic resin may be used. Examples include film packaging used; glass containers such as vials; and plastic containers such as ampoules.

The composition and agent of the present invention are preferably applied to humans, but are not particularly limited as long as the expected effects are exhibited, and can be applied to animals other than humans. .. The users of the compositions and agents of the present invention are not particularly limited, and for example, they may be healthy persons, but those who are expected to have physiological activity by proteases are preferable, and middle-aged and elderly persons aged 40 years or older are more likely. preferable. The frequency of use of the composition and the agent of the present invention is not particularly limited, and is, for example, once a week or more, preferably twice a week or more.

The blending amount of papaya and camu camu berry in the composition and agent of the present invention can be appropriately set depending on the administration form and dosage form thereof, and is not particularly limited. For example, the total amount of papaya and cam cam berry is set to 100 parts by mass as a whole, and the lower limit is 0.0001 parts by mass or more, 0.001 parts by mass or more, preferably 0.003 parts by mass or more in terms of dry mass. The upper limit is the dry mass, for example, 100 parts by mass or less, preferably 50 parts by mass or less, and more preferably 10 parts by mass or less.

In addition to the active ingredient, the composition and agent of the present invention can contain a second physiologically active ingredient exhibiting a protease activity promoting action. The second physiologically active component is not particularly limited as long as it exhibits a protease activity promoting action known so far. For example, the active ingredient of the composition or agent which exhibits the protease activity promoting action described in Patent Document 1 can be mentioned. By containing papaya and camu camu berry and a second bioactive ingredient, the composition and agent of the present invention can be a composition and agent exhibiting a synergistic protease activity promoting action. The second bioactive component can be one or more components. The blending amount of the second physiologically active ingredient is not particularly limited as long as it does not interfere with the solution of the problem of the present invention, and is appropriately adjusted.

The method for producing the composition and the agent of the present invention is not particularly limited, and the composition and the agent are produced according to a general production method known to those skilled in the art depending on the mode of use. For example, in the case of granules or solids, the papaya extract and camouflage berry fruit powder are mixed as they are or with the above other components or the second bioactive component at the same time or in several steps in a fluidized bed. It can be formed into a tablet shape by granulating according to a granulation method such as a granulation method, a stirring granulation method, or an extrusion granulation method to form granules, and further compression molding according to a conventional method using a tableting machine or the like.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples, and the present invention can take various aspects as long as the problems of the present invention can be solved. ..

It was demonstrated as follows that the composition containing papaya extract and camu camu berry fruit powder has a particularly remarkable protease activity promoting action.

(1) Test substance As the test substance, a commercially available papaya extract (proteolytic titer: NFPU / mg ≧ 6,000) and camu camu berry fruit powder were used.

(2) Preparation of tyrosine calibration curve After drying tyrosine at 105 ° C. for 3 hours, 0.500 g was accurately weighed and dissolved by adding 0.2N hydrochloric acid to make exactly 500 ml, which was used as a tyrosine standard solution. did. Accurately weigh 100 μl, 200 μl, 300 μl and 400 μl of this tyrosine standard solution, and scalpel up to 10 ml with 0.2N hydrochloric acid to prepare a calibration curve test solution.

To 2 ml of each solution of 0.2N hydrochloric acid and calibration curve test solution, 5 ml of 0.55 M sodium carbonate and 1 ml of Foline reagent were added, and the mixture was incubated at 37 ° C. for 30 minutes. Here, the Foline reagent was prepared by dissolving 5 g of sodium tungstate and 1 g of phosphoribtenic acid in 50 ml of pure water, adding 2.5 ml of phosphoric acid, refluxing and extracting, and then measuring up to 200 mL. The test was performed with a repetition rate of 2.

200 μl was transferred to a 96-well plate, and the absorbances A ₀ , A ₁ , A ₂ , A ₃ and A ₄ at 660 nm were measured. Here, the tyrosine concentrations of A ₀ , A ₁ , A ₂ , A ₃ and A ₄ are 0, 10, 20, 30 and 40 μg / ml, respectively.

Regarding the measured values, the vertical axis represents the absorbance difference ( _An −A ₀ ), and the horizontal axis represents the tyrosine concentration (μg / ml) of each solution, and a calibration curve was prepared. From the obtained calibration curve, the amount of tyrosine ([F] μg / ml) with respect to the absorbance difference of 1.000 was calculated.

(3) Measurement of protein digestibility The casein solution was prepared as follows. That is, about 1 g of casein (derived from bovine milk (Hammerson prescription); Wako Pure Chemical Industries, Ltd.) was precisely weighed, incubated at 105 ° C. for 2 hours, and then the dry weight was measured. The equivalent of 1.20 g of the obtained dried casein was precisely weighed, 160 ml of 0.05 M disodium monohydrogen phosphate was added, and the mixture was heated and dissolved in a water bath (40 ° C., about 15 minutes). A casein solution was prepared by adjusting the pH to 7.5 with 1M hydrochloric acid and measuring up to 200 ml with ultrapure water.

As a protein precipitation solution, a solution containing 0.11M trichloroacetic acid, 0.22M sodium acetate and 0.33M acetic acid was prepared.

A solution containing 0.01 M NaCl, 0.002 M calcium acetate and 0.002 M calcium sulfate was prepared as an enzyme diluted solution.

5 ml of casein solution was incubated at 37 ° C. for 10 minutes, 1 ml of test sample solution was added, and the mixture was immediately shaken. The obtained solution was incubated at 37 ° C. for 10 minutes, 5 ml of protein precipitation solution was added, and the mixture was incubated at 37 ° C. for 30 minutes and then filtered using a fold-folded filter paper (No. 5B: φ110 mm; Advantech). ..

In addition, as a blank, 5 ml of a protein precipitate solution was added to 1 ml of a sample solution and mixed, and then 5 ml of a casein solution was added to prepare a blank. After incubating at 37 ° C. for 30 minutes, a fold-folded filter paper (No. 5B: φ110 mm) was prepared. ) Was used for filtration.

To 2 ml of the filtrate, 5 ml of 0.55 M sodium carbonate and 1 ml of Foline reagent were added, and the mixture was incubated at 37 ° C. for 30 minutes. 200 μL of the incubated solution was transferred to a 96-well plate, and the absorbance ( _AT ) at 660 nm was measured. Moreover, the absorbance at a blank was A _B.

Based on the obtained absorbance, the protein digestibility was calculated using the following formula:
Protein digestion (Units _{/ g) = (A T -A} B) × F × ( amount of reaction solution) × (1/10) × (1 / W)
F: Amount of tyrosine (μg / ml) when the absorbance difference determined from the tyrosine calibration curve is 1.000.
Reaction solution: Casein solution + Test sample solution + Protein precipitation solution W: Amount of sample in reaction solution (g)

(4) Test 1: Examination of the concentration of papaya extract The papaya extract was dissolved in an enzyme diluted solution so as to be 200 mg / mL, and 0.0128, 0.064, 0.32, 1.6, 8 and 40 mg / The test sample solution was obtained by diluting to mL (common ratio 5). The protein digestibility was measured using this test sample solution.

In order to examine the papaya extract concentration suitable for the test, the test was carried out using a test sample solution prepared at 0.0128 to 200 mg / mL (n = 1). The measurement results are shown in Table 1. As shown in Table 1, protein digestibility was highest at 0.32 mg / mL and decreased concentration-dependently above 1.6 mg / mL. Therefore, the papaya extract concentration used in the following test was set to 0.32 mg / mL.

(5) Test 2: Protein digestibility of papaya extract and camouflage berry fruit powder The papaya extract solution prepared below and the camouflage fruit powder solution of each concentration were mixed in equal amounts to prepare a test sample solution. For the papaya extract solution, the papaya extract was dissolved in an enzyme-diluted solution so as to be 6.4 mg / mL, and diluted to 640 μg / mL. The cam cam berry fruit powder solution was prepared by dissolving cam cam fruit powder in an enzyme dilution solution to 6.4 mg / mL and diluting to 2.56, 6.4, 12.8 and 64 μg / mL.

Protein digestibility was measured for a test sample solution in which 320 μg / mL of papaya extract solution and camouflage berry fruit powder solution were combined (n = 3). The test results are shown in FIG. Surprisingly, the concentrations of the cam cam berry fruit powder solution to be combined with the papaya extract solution were 1.28 and 3.2 μg / mL, which were equal to or less than those of the papaya extract solution alone, but cam cam. When the concentration of the berry fruit powder solution was 6.4 μg / mL or more, about 1.2 times the protein digestibility was obtained as compared with the case of the papaya extract solution alone. These results indicate that the combination of papaya extract and camu camu berry fruit powder synergistically improves protein digestibility rather than additively.

References:
(1) Activity measurement method by notification of Central Pharmaceutical Affairs Council No. 523; Examination of protein digestibility measurement method for proteases for food production and papain preparations (2) Japan Official Association: Revised cold medicine / antipyretic analgesic test method ( Appendix 2) -Antacid / pH test method and digestive power test method for gastrointestinal drugs and their explanations-

According to the present invention, the inclusions of papaya and camu camberry having a protease activity promoting action can be obtained, and general foods and drinks, foods and drinks for specified health use, nutritional function foods and drinks, and health that are beneficial to those who expect physiological activity by proteases. It can be used as functional foods and drinks, special-purpose foods and drinks, nutritional supplements, health supplements, supplements, beauty foods and drinks, other health foods and drinks, medicinal products, cosmetics, and pharmaceuticals.

Claims (1)

Oral composition containing a papaya extract and a camu camu berry fruit powder (provided that the concentration of the camu camu berry fruit powder is less than 1/100 of that of the papaya extract. The compositions and the compositions (i) to (vi) below are excluded.
(I) Martose, Sugar Based, Gelatin, Ume Extract, Enzyme (Brazil), Barley, Red Beans, Sesame, Soybeans, Wheat, Hadakamugi (naked barley), Chickpea, Red Green Beans, Oranges, Pineapples, Bananas, apples, papayas, gummy melons, hami melons, avocados, dates, acerola berries, lemons, grapes, mangoes, star fruits, watermelons, cashew nuts, kiwi fruits, pears, acai, camouflage, potatoes, pumpkins, tomatoes, peppers. , Beats, carrots, yakon, jong pectin, rosemary, basil, chamomile, hibiscus, mint, vanilla, ginseng, agaricus blazei murill, passion flower, cinnamon, ginger, juzudama seeds, sardines, claws (Roots), Gobo, Rice (Gen), Barley, Corn, Lemongrass, Mate, Stevia, Guarana, Cassaba, Seaweed, Honey, Sugar Based, Oligosaccharides, Pectin, Citric Acid , Gummy containing rice pectin and coconut oil,
(Ii) Brown rice cycle, oat, dates, sunflower seeds, sunflower seed oil, cashew butter, cashew nuts, raisins, flaxseed, sesame, almonds, liquid sugar, brown rice, strawberry puree, low erucic acid rapeseed oil, glycerol, strawberries, apples Juice, pineapple, cashew, rice candy, acai fruit powder, purple corn extract, mangostein pencarp powerer, camcum, crow wheat flour, pumpkin seeds, sugar honey, citric acid, strawberry flavor, salt, natural fragrance, lime juice, rosemary extract, tocopherol , Snacks containing Vitamin C and Arabic gum,
(Iii) Brown rice, fructo-oligosaccharide, black curly, apple, apricot, banana, camcum, cranberry, orange, peach, raspberry, strawberry, tomato, alfalfa (moyashi), barley young leaf juice, beet leaf (green), cabbage, onion , Parsley, celery seed, papaya, red grape, broccoli, carrot, garlic, spinach, maria thistle, green tea, curcumin, red wine, kiwi carrot, lotus root, echinashi, carrageenan, thyme, rigastrum berry, rice bran (fusuma), white Strawberry, Dates, Potato, Chugokunashi, White Tea, Kuzuimo, Jerusalem Artichoke, Shiitake, Satodaikon, Cub, Califlower, Ginger, Cole Rabbi, Eshalot, Mango, Grapefruit, Apple, Pear, Honey Dumeron, Pineapple, Yellow Squash, Gooseberry Golden Kiwi fruit, nectarine, yellow squid, pumpkin, yellow fig, cantaloupe melon, yellow beet root, tangerine, lemon, yellow pepper, blueberry, blackberry, elderberry, lingonberry extract, lingonberry , Black cherry extract, fig, endive, passion fruit, purple kale, rubarb, beetroot, red chicory, eggplant, pomegranate extract, red onion, gojiberry, noni, mangostin, acai, black raspberry, bilberry, blueberry, lingonberry , Phenuglique, Guava, Watermelon, Microcrystalin Cellulose, Steeric Acid, Magnesium Stearate, Silicon Dioxide and Chelac
(Iv) water, fructose, glycerol (Vegetable Glycein), citric acid, natural fragrance, xanthan gum, chlorophyll-type complex and chlorophyllin, potassium sorbate and / or sodium benzoate, spirulina, brown algae, cystoseira canaryensis from chlorase from canary isla. Chlorella (Bulgaria), cryptomondales asian, anti-total, Darss (Norway), algae, sea lettuce, Asian ulva rigida and ulva fasciata, irish litnothamnium calcarium, dulse, mediterranean rhodymenia paimata, rock weed, American ascophilum nodosum, amino acids, spirulina and / or rice bran (Fusma), Whole food antioxidants, proprietary fiber blend, apple pectin (apple pectin), oats (fusuma), arabinogaractan, citraspectin (citrus pentin), black fragile pectin, black pectin. Rutin, citrus limon exocarp-derived hesperidin, L-glutathione, echinashi (root), thyme, boron citrate, ribonucleic acid, deoxyribonucleic acid, octacosanol, astragalus root (root), ligastrumberry, butterfly, paraaminobenzoic acid, N- Acetylcysteine, grape seed extract, neurosin, ginkgo, Koryo carrot, source-70, minerals, bee pollen, Whole food pectin complex, fruit and processed fruit, apples, apricots, bananas, camcham, cranberries, oranges, Peach, raspberry, strawberry, tomato, alfalfa (moyashi), barley young leaf juice, cabbage, kaien pepper, capiscum fruitess fruit, onion bulb, parsley, shiitake, lentinus edodes mycelia, celery seed, standard Grape, grapes, broccoli (florets), carrots (roots), garlic, reishi, gandcerma lucidum fruiting body, standardized Concentrate, spinach leaf, chlorophyll, spirulina, carotene, carrageenan, carrotene, carrageenan, carrageenan, carrageenan And a liquid composition containing rice bran (bran),
(V) Hydroxycitic acid, carnitine, taurine, cider vinegar, spirulina, chlorella, corn, algae, aosa, dars, alfalfa, barley young leaf juice, parsley, broccoli (florets), olive leaves, spinach, breath green, carragenan, oat Wheat, kale, chicory root, artichoke flower, kale, sugar cane, zucchini, dandelion leaf (green), cub leaf (green), beans, spicy sardine (green), green tea (green), cabbage, Kaien pepper, onion bulb, shiitake, celery seed, carrot (root), garlic, reishi, apple, apricot, banana, black tick, camcum, cranberry, orange, peach, raspberry, strawberry, tomato, papaya, pineapple and red wine Powdered beverages containing grape bioflavonoids, as well as (vi) Genge root (astragalus root), Ashwaganda root (ashwaganda root), Nomushitake genus (cordyceps), Holy basil leaves (holibacills) hollybacil leaves (hollybacil) At least one adaptogen selected from the group consisting of root, reishi musrooms, schizandra, and suma root, camcam, papaya, and bifidobacterium. lactobacillus acidophilus (lactobacillus acidofilus), lactobacillus acidophilus DDS-1 (lactobacillus acidofhilus DDS-1), Bulgarian lactic acid bacillus (lactobacillus bulgallicus), lactobacillus baccacillus vulgallus A composition containing at least one probiotics selected from the group. ).