JP2002257828A - Absorption accelerator and screening method thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for screening an absorption accelerator capable of effectively accelerating the absorption of functional components, the absorption accelerator obtainable by the method, and drinks, food, and medicines to which the accelerator is added. SOLUTION: Caco-2 cells derived from a human colon carcinoma are cultured on a permeable membrane to form a single-layer cell layer morphologically and functionally of the shape of small intensities. Through the use of an intestinal absorption model equilibrated by adding a buffer solution of pH 6.0 to the side of a mucous membrane and a buffer solution of pH 7.4 to the side of a basement membrane and forming an H<+> gradient similar to that of an organism at intestinal absorption, the amount of fluorescent markers which transmit from the side of the mucous membrane to the side of the basement membrane under the presence of a substance to be tested is measured. Drinks, food, and medicines of which the absorption is accelerated by the addition of extracts of spinach, galangal, Japanese ginger, leek, marigold, jasmine, Acer nikoense, Salsola komarovii, dried fish larvae, hops, cordyceps, black pepper, cardamom, back tea, and loofah in which absorption accelerating activity has been discovered are prepared.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for screening an absorption-promoting substance, and more particularly, to a method for lucifer yellow (Lucife yellow) as a plurality of fluorescent markers having different absorption mechanisms.
r Yellow), Sodium Fluorescein (Sodium Fluor
escein) and rhodamine (Rhodamine), etc., individual screening methods for absorption enhancers having different absorption mechanisms, and spinach, galangal, myogyo, leek, marigold, jasmine, megsuri trees obtained by such screening. Okahijiki, whitebait,
Absorption enhancers containing, as an active ingredient, one or more selected from hops, cordyceps, black pepper, cardamom, black tea, hechima or their processed products, and minerals, monocarboxylic acids, flavonoids containing these absorption enhancers The present invention relates to foods and drinks, pharmaceuticals, and the like, in which the absorption of orally ingested functional ingredients, which are added to and blended with foods and drinks and pharmaceuticals containing preferred functional ingredients such as foods, vitamins, polyphenols, and carotenoids, are promoted.

[0002]

2. Description of the Related Art Antioxidants such as vitamins and flavonoids suppress cancer cell growth, platelet aggregation, and mast cell histamine through the action of eliminating active oxygen involved in the development of various diseases. It has been reported that it exerts many physiological effects such as inhibition of release. Thus, while the research on the physiological effects of food components taken daily is being actively conducted recently, the consumed food components are digested and absorbed, and how their physiological functions are exhibited in vivo. There were many unclear points about what to do. For example, with regard to flavonoids, even catechin, which is relatively quickly absorbed, absorbs about 5 to 8% of the intake, and about 2% of catechin moves into the blood. 5-20% of the amount, the absorption amount of theaflavins etc. is reported to be much lower (Yoshio Miyazawa, Chemistry and Biology,
38, 104, 2000), and there has been a strong demand for improvements in the absorption efficiency and in vivo use efficiency of these functional components.

[0003] In addition, minerals such as calcium, for which the necessity of ingestion is strongly recognized, are also used for the purpose of improving the absorption efficiency.
2655), gelatin and collagen degradation products (JP-A-11-318390), fructooligosaccharides (Japanese Society of Nutrition and Food Science, 52, 387, 1999) and β
-Gluco-oligosaccharide (JP-A-11-299453)
Various calcium absorption promoters have been developed and proposed. For example, casein phosphopeptide exerts an effect of promoting absorption of calcium by absorbing the peptide chelated with calcium into the body itself, so that minerals other than calcium cannot be expected to have much effect of promoting absorption. It is said that sugars and dietary fiber such as fructooligosaccharides reduce the pH in the intestinal tract by promoting fermentation of intestinal bacteria and improve the solubility of calcium that easily precipitates, so that absorption is promoted.
There is a problem that it is difficult to exert a sufficient effect depending on these, and further improvement is aimed at by seeking a more effective calcium absorption promoter by a different mechanism.

[0004] Carotenoids, which are contained in green-yellow vegetables and fruits, and are known to have cancer-preventing, immunostimulatory and anti-aging effects, are not absorbed but are excreted in feces without absorption. It has been said (Tanimura Akio et al., Handbook of Bioactive Substances in Plant Resources, 73, 1998), and there has been a demand for an improvement that increases the absorption efficiency in the body and exerts more effects.

[0005] In the pharmaceutical field, there is a strong demand for improving the efficiency of orally administered drugs in the body by improving their absorption efficiency, and studies focusing on the intestinal tract mainly involved in digestion and absorption have been vigorously conducted. Was. As a result, EDTA
And capric acid (Tomita M.etal, J. Phar. Sci. 85, 60
8,1996), polyethylene glycol (JP-A-2000-2)
For example, the use of absorption enhancers in the intestinal tract has been reported, and attempts to further improve absorption promotion activity, safety, and economy have been sought. As with pharmaceuticals, attempts have recently been made to search for intestinal absorption promoting substances from food components.

[0006] The process in which food ingested is taken into the body for the first time and is recognized is mainly the digestive and absorption process in the intestinal tract. Except for major nutrients, the absorption mechanism has been previously clarified. Although many parts did not, research and knowledge on the absorption mechanism of various components in the intestinal tract have recently been accumulated. The inner wall of the intestinal tract (small intestine) is covered with villi, and there is a monolayer of epithelial cells on the surface of the villi. Transport of nutrients and other substances is carried out through this cell layer, mainly through transporters. Intracellular transport (transport by transporters specific to each of the major nutrients such as glucose, amino acids and dipeptides), passive intracellular diffusion (specific binding of hydrophobic substances such as fat-soluble vitamins to move inside cells) Transport to the basement membrane side via proteins), intracellular transport via intracellular vesicles (transcytosis of hydrophilic macromolecules such as proteins taken up by intracellular vesicles) Transport) and passive diffusion through the intercellular space (transport by passive diffusion through the epithelial cell space, which is considered to be important as a water-soluble small molecule permeation pathway). Makoto, nutrition and health of the life sciences, 3,74,199
8).

[0007] Intracellular transport via the above-mentioned transporters includes transporters and antiporters specific to permeating substances, and a group of transporters of amino acids and water-soluble vitamins, monocarboxylic acid transporters, and the like. Many transporters, such as phosphate transporters and peptide transporters, are being elucidated rapidly along with their genes. Recently, as factors that determine or change the absorption of various nutrients or drugs,
Interest is growing (Hiroaki Yuasa et al., History of Medicine, 19
7, 3, 2001, Hitoshi Endo, Protein Nucleic Acid Enzyme, 46,583,2
001, Tsuji A. et al. Pharm. Res. 13, 963, 1996)

[0008] The path of passive diffusion through the intercellular space is
The specificity of the permeating substance is low, and it has received little attention in terms of nutritional physiology, but recently, water-soluble low-molecular substances represented by minerals such as calcium and biologically active oligopeptides derived from foods It has become evident that it is very important as a permeation path of, and it is said that tight junction controls the permeation of the substance in this path. One of the main functions of such a tight junction is to provide a barrier function to a cell layer by firmly adhering cells to each other, but also has a function of transmitting a substance useful for living organisms. Shimizu et al. Searched for a component having a tight junction regulating activity, and reported capsianoside, a diterpene glycoside of shido, and a protein of Enoki mushroom (Masashi Shimizu, Protein Nucleic Acid Enzyme, 44, 46, 1999).
However, they have not been used as materials for promoting absorption because they are unstable to heat and acids, proteins are degraded by proteases, and their absorption promoting activity is insufficient.

In addition, hydrophobic substances such as lipid-soluble substances of low polarity in the above-mentioned passive intracellular diffusion are relatively easily penetrated through cell membranes and taken into cells, but P-glycoproteins are responsible for them. The body is positively discharged as a foreign substance by the discharge pump function of the living body. For example, relatively low-polarity hydrophobic food ingredients such as fat-soluble vitamins, polyphenols, and carotenoids,
Fat-soluble and poorly-soluble drugs such as thiazolidinedione compounds and β-receptor blockers such as acebutolol and ceriprolol, which are widely used as antidiabetic drugs, are easily taken up through cell membranes, but P-glycoprotein Is actively excreted into the body by (Te
rao T et al, J. Pharm. Pharmacol. 48, 1083, 1996),
As a result, the efficiency of absorption into the body decreases. Therefore, in order to make these hydrophobic substances more effective,
Although it is always required to increase the efficiency of absorption into the body, there has been no report on a material that improves the absorption of a hydrophobic substance easily excreted by P-glycoprotein.

By the way, spinach, myoga, and chive are commonly used as vegetables, and spinach is also used as a raw material for vegetable juice. Galangal (Japanese name: Ryokyo) is a plant belonging to the family Ginger, and is prized as a medicinal and incense in the old days. At present, the rhizome is used as an edible seasoning, and is often used in curry dishes in Southeast Asia. Marigold (Japanese name: calendula), a herb commonly cultivated recently at home, is asteraceae
(Compositae) plant, flowers are used for food. Jasminum officinale L. (Asteraceae) is a plant of the Oleaceae family, and jasmine tea flavored with its flowers is well known.

Meguri tree is a Japanese maple tree, also known as butterflies and honeysuckle. It mainly contains epi-rhodendrin in the bark, leaves and twigs, and is said to be good for eye diseases. It is also said to have an effect on the liver. The aqueous solution to which the dried raw material with the bark of Meglinoki was added was added to a high pressure kettle for 1 hour.
After extracting Meglinoki extract at a temperature of 00 ° C or higher,
Remove raw materials, sterilize at a temperature of more than 121 ℃,
Next, drinks, udon, buckwheat, candy, rice, or rice porridge using a megsuri tree extract from which insoluble materials have been removed by filtration are known (Japanese Patent Application Laid-Open No. Hei 8-242815). Okahijiki is a herb of the family Cruciferae rich in vitamins and minerals, and has long been used as an edible vegetable in Japan. Shirasu that is often displayed at home dining tables is generally a juvenile fish of the Anchovy family, and is often distributed in a dried and dried state. Hops (Japanese name: Karahanasou) are dioecious plants of the family Hemp and only female strains are cultivated. Female lupulin is one of the indispensable ingredients that gives the bitterness and aroma of beer. It is said that lupulin also has effects such as diuresis, healthy stomach and sedation.

[0012] Cordyceps is a plant in which ascomycetes ergot fungi, Fumus sinenthus mushroom, originally parasitized insects such as lepidoptera, especially bats, and produced sclerotia and fruiting bodies in the body. It is prized as a traditional Chinese medicine.
In Japan, a group of mushrooms parasitic on insects and spiders is generally called cordyceps, and it is said that 250 species, such as semi-take, hanasanagitake, and turtle mushroom, inhabit. According to recent studies, Cordyceps has effects on the central nervous system (sedative effect), effects on the immune system, effects on blood vessels (prevents arteriosclerosis), nourishing tonic effects, hypoglycemic effects, etc. In particular, it is expected to be used as an anticancer drug. Black pepper is a tropical plant belonging to the family Pepper, which is obtained by picking immature fruits just before they start to color and drying the whole skin. It is the most popular spice widely used in cooking around the world. Cardamom (Japanese name:
(Jozuku) is a ginger family plant that extracts seeds from fruits (fruits) and uses them mainly as spices in various dishes. Hechima is a vine annual belonging to the Cucurbitaceae family, and in some regions, young fruits are eaten as boiled dishes. Black tea is known as a fermented tea involving microorganisms. Specifically, “Awa late tea” and “Goishi tea (Otoyo-cho, Kochi)” and “Mian tea” in the Yunnan region of China and mountainous regions in northern Thailand. "Repet tea" and the like (JP-A-11-276072).

[0013]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems of the prior art and to use a safe and relatively inexpensive food material which is taken daily to absorb functional components preferable for the human body. A screening method for an absorption enhancer that effectively promotes and improves utilization efficiency, in particular, an individual screening method for an absorption enhancer having a different absorption mechanism, an absorption enhancer obtained by such a screening method, and the addition of these absorption enhancers An object of the present invention is to provide a food / beverage product / medicine capable of promoting absorption of a functional component taken orally.

[0014]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and have obtained safety and stability from many foods that have been conventionally ingested, as well as intestinal tracts. Considering that it is sufficient to select a food material that remarkably promotes absorption, an intestinal absorption model modified so as to more closely match intestinal absorption, that is, a human intestinal cell culture Caco-2
Using an intestinal absorption model to select a plurality of fluorescent markers with different absorption mechanisms and use them individually,
A new screening method has been developed to individually screen for absorption enhancers with different absorption mechanisms. As a fluorescent marker having a different absorption mechanism, lucifer yellow, assuming screening of an absorption promoting substance for a hydrophilic substance that is passively diffused from the mucosal side to the basement membrane side through the intercellular space, Sodium fluorescein, assuming the screening of an absorption-promoting substance for a hydrophilic substance that is absorbed from the mucosal side to the basement membrane side in an energy-dependent manner via cells such as transporters,
Rhodamine, assuming screening of an absorption promoting substance for a hydrophobic substance in the intracellular passive diffusion pathway,
Each was used. Rhodamine has low polarity, and P
-Is known to be excreted by glycoproteins (Hsings S. et al, Gastroenterology, 102, 879, 1992, S
akai M. et al, J. Pharmaceutical Sci., 86,779,199
7).

Using the individual screening method for absorption promoting substances having different absorption mechanisms, the absorption promoting activity of 300 or more food materials was energetically evaluated for each fluorescent marker. (LY: excitation 430 nm, detection 535 nm) by spinach, galangal, myoga, chive, marigold, jasmine, megsuri tree, okahiji, whitebait, hops, and cordyceps extracts (LY absorption promoter group) In addition, sodium fluorescein (FC:
Screening using excitation 492 nm, detection 515 nm) significantly absorbed the black pepper, cardamom, and black tea extracts, respectively, and screening using rhodamine (RH: excitation 505 nm, detection 540 nm) to the extract of Hichima. It has been found to have promoting activity.
Furthermore, the above-mentioned LY absorption promoting substance group is composed of calcium or an oligopeptide (Gln-Gln-G
In-Pro-Pro), quercitrin, and naringin (flavonoids) were confirmed to significantly promote absorption, and the present invention was completed.

That is, the present invention relates to Ca
The co-2 cells are cultured on a permeable membrane to form a small intestinal-like monolayer of cells morphologically and functionally, with a pH of 6.
A buffer solution of pH 7.4 and a buffer solution of pH 7.4 were added to the basement membrane side to form an H ⁺ gradient similar to that at the time of absorption into the intestinal tract of a living body and equilibrated. Measure the resistance value (TER), and determine that a cell is determined to have a sufficient tight junction (TER ≧ 200Ω · c
m ² ), and the selected Caco-2 cells
Using a plurality of fluorescent markers having different absorption mechanisms prepared with a buffer solution of 6.0 individually, a test substance also prepared with a buffer solution of pH 6.0 was added to the mucosal side, and the basement membrane from the mucosal side was added. The amount of the fluorescent marker per fixed area per unit time, which is transmitted to the side, is measured individually at a wavelength suitable for each fluorescent marker using a fluorimeter. Screening method (Claim 1)
And two or three types of fluorescent markers selected from lucifer yellow (LY), sodium fluorescein (FC) and rhodamine (RH) as a plurality of fluorescent markers having different absorption mechanisms.
The method for individual screening of absorption promoting substances having different absorption mechanisms described in claim 2 (Claim 2).
Two cells are cultured on a permeable membrane to form a morphologically and functionally small intestinal monolayer of cell layer, a pH 6.0 buffer on the mucosal side and a pH 7.4 buffer on the basement membrane side. Was added to form a H ⁺ gradient similar to that at the time of intestinal absorption in the living body and equilibrated, and then the transepithelial electric resistance value (TE
R) is measured, and cells judged to have a sufficient tight junction formed (TER ≧ 200Ω · cm ² )
Was added to the selected Caco-2 cells, and a fluorescent marker consisting of sodium fluorescein prepared with a buffer solution of pH 6.0 and a test substance also prepared with a buffer solution of pH 6.0 were added to the mucosa side. A method for screening an absorption-promoting substance, characterized in that the amount of a fluorescent marker per fixed area for a certain period of time permeating from the mucosal side to the basement membrane side is measured by a fluorometer (claim 3); 4. The composition according to claim 1, wherein the composition has substantially no toxicity.
(Claim 4).

Further, the present invention contains, as an active ingredient, a combination of absorption promoting substances having different absorption mechanisms, which are obtained by the screening method using a plurality of fluorescent markers having different absorption mechanisms individually according to claim 1 or 2. A combination of a total absorption enhancer (claim 5) and a combination of absorption enhancers having different absorption mechanisms obtained by a screening method using lucifer yellow as a fluorescent marker; As two or three or more absorption mechanisms selected from the group of FC absorption promoting substances obtained by the screening method using sodium fluorescein and the group of RH absorption promoting substances obtained by the screening method using rhodamine as a fluorescent marker, respectively. 6. A combination of different absorption enhancing substances. Overall absorption enhancer of the mounting (claim 6)
And the LY absorption promoting substance group is selected from spinach, galangal, myoga, chive, marigold, jasmine, meguri tree, okajiki, whitebait, hops, cordyceps, or their treated products, and the FC absorption promoting substance group is black. pepper,
RH selected from cardamom, black tea or their processed products
7. The total absorption enhancer according to claim 6, wherein the group of absorption promoting substances is selected from a henchma or a processed product thereof, and the processed product is an extract. An absorption enhancer (claim 9) obtained by the screening method using sodium fluorescein as a fluorescent marker according to claim 3 or 4, spinach, galangal, An absorption enhancer comprising, as an active ingredient, one or more selected from myoga, chive, marigold, jasmine, megsuri tree, oakhiji, whitebait, hops, cordyceps, or a treated product thereof. (Claim 10) or one or two selected from black pepper, cardamom, black tea or a processed product thereof as an active ingredient. The absorption enhancer (Claim 12) wherein the absorption enhancer contains a henchma or a processed product thereof as an active ingredient, and the treated product is an extract. Item 13 relates to the absorption enhancer according to any one of Items 10 to 12 (Claim 13).

The present invention also relates to the absorption of a functional ingredient taken orally, characterized in that the total absorption enhancer according to any one of claims 5 to 8 is added to or blended with a food or drink containing a preferred functional ingredient. Food and drink that can promote
4) In addition, 0.2 to 30% by weight of the total absorption enhancer as a solid content in the extract is added and blended, and the absorption of the functional ingredient taken orally according to claim 14 is promoted. Food and drink that can be used (Claim 15) and Claim 1
A food or drink capable of promoting the absorption of orally ingested functional components, characterized in that the absorption enhancer according to 0 or 13 is added to or blended with a food or drink containing a preferred functional component (Claim 16) A food or drink capable of promoting the absorption of orally ingested functional components, characterized in that the absorption enhancer according to claim 9, 11, or 13 is added to or blended with a food or drink containing a preferred functional component. The absorption enhancer according to claim 17) or claim 12 or 13 is added to or blended with a food or drink containing a preferred functional component, thereby facilitating the absorption of an orally ingested functional component. The oral composition according to any one of claims 16 to 18, wherein the food or drink (Claim 18) and the absorption enhancer are added and blended in an amount of 0.2 to 30% by weight as a solid content in the extract. Absorption of ingested functional ingredients The food or beverage that can be promoted (Claim 19) and the preferred functional component are one or more components selected from minerals, monocarboxylic acids, flavonoids, vitamins, polyphenols, and carotenoids. A food or drink capable of promoting the absorption of a functional ingredient taken orally according to any one of claims 14 to 19 (claim 20).

Further, the present invention provides a method for improving the absorption of orally ingested functional components, characterized in that the total absorption enhancer according to any one of claims 5 to 8 is added to and blended with a drug containing a preferred functional component. Absorption of a functional ingredient taken orally, characterized by adding or blending a drug capable of promoting (claim 21) or an absorption enhancer according to claim 10 or 13 to a drug containing a preferred functional ingredient. Orally ingested function, which is obtained by adding and blending a drug capable of accelerating the absorption (claim 22) or the absorption enhancer according to claim 9, 11, or 13 to a drug containing a preferable functional component. A drug capable of promoting the absorption of the component (claim 23) or the absorption enhancer according to claim 12 or 13;
Pharmaceuticals capable of promoting absorption of orally ingested functional components characterized by being added to or blended with pharmaceuticals containing preferred functional components (claim 24), and preferable functional components are minerals and monocarboxylic acids 25. The composition according to any one of claims 21 to 24, wherein the flavonoids, vitamins, polyphenols, and carotenoids are one or more components. Drugs that can be used (Claim 2
Regarding 5).

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION When Caco-2 cells derived from human colon cancer are cultured on a permeable membrane, a small intestine-like monolayer cell layer is formed morphologically and functionally, and the results in the human body are improved. It has been widely recognized as an experimental system that reflects on humans, and is currently used by many researchers as a model of intestinal absorption in the living body (Chemistry and Biology, 37, 326, 1999). The screening method of the present invention is an improved intestinal absorption model using Caco-2 cells, and can be broadly classified into two methods. 1
One is a method of individually screening for a plurality of absorption enhancers having different absorption mechanisms by individually using a plurality of fluorescent markers having different absorption mechanisms in place of various functional components preferable for the human body. An overall absorption enhancer combining absorption enhancers with different absorption mechanisms can be obtained. The other is a screening method for a monocarboxylic acid transporter absorption promoting substance using sodium fluorescein as a fluorescent marker, which is one of the screening methods constituting an individual screening method for the absorption promoting substance having a different absorption mechanism.

The individual screening method of the absorption promoting substance having a different absorption mechanism according to the present invention includes culturing Caco-2 cells derived from human colon cancer on a permeable membrane and morphologically and functionally reducing the intestinal appearance. Form a monolayer of cell layer, p
After adding a buffer solution of H6.0 and a buffer solution of pH 7.4 to the basement membrane side to form an H ⁺ gradient similar to that at the time of intestinal absorption of a living body and equilibrating the same, the passage of Caco-2 monolayer cells was performed. Epithelial electric resistance (TER) is measured, and cells (TER ≧ 200Ω) determined to have a sufficient tight junction are formed.
· Cm ² ), and p is added to the selected Caco-2 cells.
Using a plurality of fluorescent markers having different absorption mechanisms prepared with a buffer solution of H6.0 individually, a test substance also prepared with a buffer solution of pH 6.0 was added to the mucosal side, and the basement membrane from the mucosal side was added. The screening method is not particularly limited as long as it is a screening method for individually measuring the amount of a fluorescent marker per fixed area per unit time at a wavelength suitable for each fluorescent marker using a fluorometer. Using an intestinal absorption model in which the same H ⁺ gradient was formed as in the intestinal absorption of
The test substance and each fluorescent marker are individually present on the mucosal side, and the amount of the fluorescent marker penetrating from the mucosal side to the basement membrane side is measured, and the measured value is used for the control in the absence of the test substance. By comparing the values with the values, it becomes possible to individually screen the absorption promoting substances having different absorption mechanisms.

As the plurality of fluorescent markers having different absorption mechanisms, two or three types of fluorescent markers selected from lucifer yellow, sodium fluorescein and rhodamine can be preferably exemplified. For the test food material group, using lucifer yellow as a fluorescent marker, screening for a substance that promotes absorption of a hydrophilic substance or the like by a passive diffusion pathway through intercellular spaces, a transporter using sodium fluorescein as a fluorescent marker, etc. Screening of substances that promote the absorption of hydrophilic substances that are absorbed from the mucosal side to the basement membrane side in an energy-dependent manner through cells, and absorption of hydrophobic substances by the intracellular passive diffusion pathway using rhodamine as a fluorescent marker Substances that promote Of the screening can be a method of performing at least two screening. Fluorescent markers include Lucifer Yellow, Sodium Fluorescein, Rhodamine, FI
TC (fluorescein isothiocyanate), TRIT
C (tetramethylrhodamine isothiocyanate), C
A fusion protein obtained by fusing a fluorescent substance such as y3 (cyanine-3) or a fluorescent protein such as GFP (green fluorescent protein) can also be used. Also, instead of the fluorescent marker, an enzyme marker such as HRP or a marker labeled with a radioactive substance can be used.

The concentration of a test substance or a fluorescent marker in such screening may be selected as desired, taking into account sensitivity and precision, as long as it does not adversely affect cells. ~ 5mg / m
1 and a concentration of 20 to 500 μg / ml can be generally indicated, but for Lucifer Yellow, 300 to
500 μg / ml, preferably 350 to 450 μg / m
l, especially at concentrations around 400 μg / ml, for sodium fluorescein, 30-50 μg / m
1, preferably 35-45 μg / ml, especially 40 μg / ml
When used at a concentration of about 10 ml, rhodamine is 40
２００200 μg / ml, preferably 50-100 μg / m
1, especially at a concentration of around 100 μg / ml, screening can be performed with high sensitivity and accuracy.

As a method for screening the absorption promoting substance of the present invention using sodium fluorescein as the fluorescent marker, Caco-2 cells derived from human colon cancer are cultured on a permeable membrane and morphologically and functionally in small intestine. And a buffer solution of pH 6.0 is added to the mucosa side and a buffer solution of pH 7.4 is added to the basement membrane side to form the same H ⁺ gradient as in the intestinal absorption of the living body. After equilibration, the transepithelial electrical resistance value (TE
R) is measured, and cells judged to have a sufficient tight junction formed (TER ≧ 200Ω · cm ² )
Was added to the selected Caco-2 cells, and a fluorescent marker consisting of sodium fluorescein prepared with a buffer solution of pH 6.0 and a test substance also prepared with a buffer solution of pH 6.0 were added to the mucosa side. It is not particularly limited as long as it is a method for screening an absorption-promoting substance in which the amount of a fluorescent marker per unit area is measured by a fluorometer for a certain period of time permeating from the mucosal side to the basement membrane side. Using an intestinal absorption model in which the same H ⁺ gradient was formed as described above, the test substance and sodium fluorescein were present on the mucosal side, and the amount of sodium fluorescein permeating from the mucosal side to the basement membrane side was measured. By comparing the value with the value of the control in the absence of the test substance, it becomes possible to screen for the absorption enhancing substance.

The buffer used in the screening method of the present invention is not particularly limited, but has a buffering ability in the range of pH 6.0 to pH 7.4, and maintains the osmotic pressure balance to maintain cell metabolism. Preferably, the buffer can supply necessary energy for the reaction. Examples of such a buffer include HBSS buffer (Glucose 0.1%, NaC
l 0.8%, CaCl ₂ 0.014%, NaHCO ₃
0.035%, KCl 0.04%, KH ₂ PO ₄ 0.0
06%, MgSO ₄ 0.0098%, Na ₂ HPO ₄
0.0048%), and the HBS
The pH of the S buffer can be adjusted by appropriately using a synthesis buffer such as HEPES or MES and NaOH or HCl. In the screening method of the present invention, the HBSS buffer (pH 6.
0), by adding HBSS buffer (pH 7.4) to the basal membrane side, similar H ⁺ gradient and during intestinal absorption of the living body is formed, the absorbent material that is transported H ⁺ gradient as the driving force Can also be evaluated, so that an excellent intestinal absorption model can be obtained.

As the absorption-promoting substance to be subjected to the screening method of the present invention, an absorption-promoting substance having substantially no cytotoxicity is preferable. By selecting a substance that has substantially no cytotoxicity from the substances screened as the target, or by selecting a substance that has substantially no cytotoxicity in advance as the test substance in the screening of the absorption promoting substance Can be. The presence or absence of cytotoxicity is determined by measuring LDH release rate% using LDH (lactate dehydrogenase) -cytotoxicity test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) or the like, as described in Examples below. It can be evaluated by measuring the rate of respiratory inhibition using Alamar Blue test solution (Iwaki Glass Co., Ltd.) or the like.

The total absorption enhancer of the present invention contains, as an active ingredient, a combination of absorption enhancers having different absorption mechanisms obtained by the above-mentioned screening method using a plurality of fluorescent markers having different absorption mechanisms individually. Any substance may be used, for example, a LY absorption promoting substance group obtained by a screening method using lucifer yellow as a fluorescent marker, and an FC absorption promoting substance group obtained by a screening method using sodium fluorescein as a fluorescent marker And a combination of two or three or more absorption enhancers having different absorption mechanisms selected from the RH absorption enhancer group obtained by the screening method using rhodamine as a fluorescent marker (for example, two kinds from the LY absorption enhancer group) , One from the FC absorption promoting substance group, RH absorption And the like. The above-mentioned LY absorption-promoting substance group includes spinach, galangal, myoga, chive, marigold, jasmine, and megsuri. Trees, okajiji, whitebait, hops, cordyceps, or their processed products are included, and the FC absorption promoting substance group includes black pepper, cardamom, black tea or these processed products,
The group of RH absorption promoting substances includes hemlock or a processed product thereof. Further, as the total absorption promoter of the present invention, the above-mentioned LY
In addition to the absorption-promoting substance group, the FC-absorption-promoting substance group, and the RH-absorption-promoting substance group, an absorption-promoting substance in the intracellular transport pathway via a transporter specific to each of the main nutrients such as glucose, amino acids, and dipeptides is described. It can also be blended.

As the absorption enhancer of the present invention, one or two selected from spinach, galangal, myoga, chive, marigold, jasmine, meguri tree, okajiki, whitebait, hops, cordyceps, or a treated product thereof
An absorption enhancer containing at least one species as an active ingredient, an absorption enhancer obtained by a screening method using sodium fluorescein as the fluorescent marker such as black pepper, cardamom, black tea or a processed product thereof, or a henchma or a processed product thereof And an absorption accelerator mainly for a hydrophobic functional component containing as an active ingredient.

[0029] In addition, the processing method of spinach, galangal, myoga, chive, marigold, jasmine, meguri tree, okajiki, whitebait, hop, cordyceps, black pepper, cardamom, black tea, hemachima, etc. is particularly preferable. It is not limited, and examples thereof include an extraction process, a grinding process, a crushing process, and a pressing process, and these processes may be used in combination. Among these treatments, the extraction treatment is preferable, and the extraction solvent used in the extraction treatment is not particularly limited, but those usable in the food industry are preferable, and relatively room temperature or heated water, alcohols such as ethanol, etc. A highly polar solvent can be suitably exemplified. In addition, the processed materials such as the extract may be subjected to purification processing such as deodorization and decolorization processing, separation / fractionation processing by chromatography and the like, concentration processing, pasting processing, drying processing, and dilution, as necessary. Post-treatment such as a chemical treatment can also be performed.

And also, spinach, galangal, myoga, chive, marigold, jasmine, megsuri tree, oakhiji, whitebait, hops, cordyceps, black pepper,
Substances such as cardamom, black tea, and hemchima can be used in their entirety, but it is preferable to use parts that are usually used for eating and drinking. For example, spinach can use stems and leaves other than roots.Megsuri trees mainly use bark, okahijiki stems and leaves other than roots, etc. To
Hops can use cones and leaves other than roots, and jasmine and black tea can use the tea leaves. In addition, fruits, flowers and stems other than roots and leaves can be used up to the hem.

The total absorption enhancer or absorption enhancer of the present invention comprises:
It is desirable to be taken almost simultaneously with a preferred functional component for the human body, and it is preferable to take the total absorption enhancer or absorption enhancer of the present invention at the time of or before intake of foods and drinks or pharmaceuticals containing the preferred functional component. . As described above, the total absorption enhancer and the absorption enhancer of the present invention can be separately ingested with foods and drinks or pharmaceuticals containing functional components preferable for the human body. It can be added to and blended with foods and drinks and pharmaceuticals containing functional components preferable for the human body, and used as foods and drinks and pharmaceuticals in which the absorption of functional ingredients taken orally is promoted, and such embodiments are also included in the present invention. Is done. Such foods and drinks and pharmaceuticals in which the absorption of the orally ingested functional component of the present invention is promoted include the above-mentioned comprehensive absorption enhancer and absorption enhancer of the present invention, and foods and drinks and pharmaceuticals containing functional components preferable for the human body. It is not particularly limited as long as it is a food and drink or a pharmaceutical obtained by adding to the above, but as the total absorption enhancer or absorption enhancer to be added to and blended with the food or drink or the pharmaceutical, the absorption promoting activity is more. An enhanced form, for example, a form suitable for each absorption enhancer such as a concentrate, a paste, a dried product, a diluted product, or the like is preferable.

The functional components preferable for the human body in the present invention include, for example, minerals such as calcium, monocarboxylic acids such as butyric acid which are energy sources of the intestinal tract, flavonoids such as quercitrin, water-soluble vitamins, antiallergic drugs, and hypotensive drugs. And hydrophilic functional components such as oligopeptides exhibiting various physiological effects such as anti-diabetic effects, and hydrophobic functional components such as fat-soluble vitamins, polyphenols and carotenoids. Foods and drinks originally containing these preferred functional components, and foods and drinks and pharmaceuticals to which these preferred functional components have been added / blended, and the total absorption enhancer or absorption enhancer of the present invention is added / blended, if necessary. Further, the food and drink or the pharmaceutical product of the present invention, which has been subjected to desired processing, can be used as, for example, ordinary general foods, health foods, foods for patients, function improving agents, and the like. The food or drink of the present invention may be in any form of solid (solid, powder, granule, etc.), paste, liquid, or suspension, and may be used in a desired form as appropriate. It is possible. In the case of pharmaceuticals, administration in the form of tablets, capsules, granules, powders and the like can be considered.

The amount of the total absorption enhancer and the absorption enhancer of the present invention added to foods and drinks and pharmaceuticals containing functional components preferable for the human body depends on the content of the functional component in various foods and drinks and pharmaceuticals and the total absorption enhancer. And the type of absorption enhancer, etc., cannot be determined unconditionally, but it is preferably within the range that does not impair the taste and quality of foods, beverages, pharmaceuticals, etc. to which the total absorption enhancer or absorption enhancer is added or blended. Is preferably added and blended in an amount corresponding to 0.2 to 30% by weight as a solid content in the extract.

[0034]

EXAMPLES The present invention will be specifically described below with reference to examples, but the technical scope of the present invention is not limited by the contents of the examples. Example 1 (Preparation of intestinal absorption model) Caco-2 cells (ATCC HTB-37, manufactured by Dainippon Pharmaceutical Co., Ltd.) were transfected at 37 ° C. in Transwell (Costar) using DMEM (Dulbecco's modified Eagle medium). After culturing for about a week, the medium was removed from the cultured Caco-2 cell plate, and the mucosal wells were washed several times with HBSS buffer (pH 6.0) and the basement membrane wells were washed several times with HBSS buffer (pH 7.4). Washed. Next, H
A BSS buffer (pH 6.0) and an HBSS buffer (pH 7.4) were added to the basement membrane side to form an H ⁺ gradient similar to that at the time of absorption into the intestinal tract of a living body. After equilibration, Millicell-ERS
TER of Caco-2 monolayer cells (Millipore)
Was measured, and cells (TER ≧ 200Ω · cm ² ) judged to have a sufficient tight junction were selected and used for the next screening.

Example 2 (Preparation of test sample) Carrot, spinach, watercress, celery, okajiki, parsley, lettuce, aloe, cabbage, broccoli, paprika, pumpkin, bell pepper, hichima, cauliflower, spring chrysanthemum, shishito, leek, Vegetables such as myogyo, shallots and beets, green tea, black tea, black tea, Tochu tea, dokudami tea, mulberry leaf tea, mugwort tea, gymnema tea, turmeric tea, jasmine tea, etc., walnuts, prunes, megsuri tree , Figs, persimmons, pomegranates, pomegranates, citrons, citrons, wolfberry and other fruits and tree nuts, cinnamon, cardamom, coriander, galangal, black pepper, pepper, nutmeg, cloves, rosemary, hops, chamomile, linden, marigold, etc. Herbs and spices, enoki, shimeji, maitake mushroom, eryngii, nameko, cordyceps Grass, pine mushrooms, Chaga, Agaricus, mushrooms and whitebait, such as, scallops, etc., was a candidate material and selected a total of more than 300 food material. After extracting these candidate materials with hot water of 85 ° C. or higher for 20 minutes, this extract was freeze-dried. This dry solid was dissolved in HBSS buffer pH 6.0 to prepare a test sample.

Example 3 (Verification of FC or LY Absorption Mechanism -Effect of Mucosal pH-) HBSS buffer pH 7.4 was added to the basement membrane side well of the Caco-2 cell layer, and the mucosal side well was added. For HBSS, fluorescent markers prepared at the respective pHs of HBSS buffer pH 6.0, 6.5 and 7.4 were added. As a fluorescent marker, 40
0 μg / ml lucifer yellow (LY: excitation 430)
nm, detection 535 nm), 400 μg / ml sodium fluorescein (FC: excitation 492 nm, detection 515)
nm), the amount of the fluorescent marker that permeates from the mucous membrane side to the basement membrane side at 37 ° C. over time is measured using a fluorometer (Molecu
lar Devices "spectra MAX GEMINI"). FIG. 1 shows the permeation amount of the fluorescent marker FC over time, and FIG. 2 shows the permeation amount of the fluorescent marker LY over time. As can be seen from FIGS. 1 and 2, FC significantly increases the amount of permeation as the mucosal pH decreases, whereas LY increases the mucosal pH.
Showed almost the same transmission amount without being affected by the above. That is, when an H ⁺ gradient is generated between the mucosal side and the basement membrane side, FC and LY are generated.
It was shown that there was a large difference in the permeation absorption mechanism of the agar.

Example 4 (Verification of FC or LY Absorption Mechanism-Permeation Direction-) HBSS buffer pH 7.4 was added to the basement membrane side well, and HBSS buffer pH 6.0 was added to the mucosa side well. An experiment (forward direction) to which the prepared fluorescent marker was added, and an experiment in which HBSS buffer pH 6.0 was added to the mucosal side well and the fluorescent marker prepared with HBSS buffer pH 7.4 was added to the basement membrane side well. Sections (reverse direction) were provided at the same time, and the directionality of the transmission and absorption of the fluorescent marker was verified. As a fluorescent marker, Lucifer Yellow (LY: excitation 430 nm, detection 535 nm) and 400 μg / ml were used.
Using 00 μg / ml sodium fluorescein (FC: excitation 492 nm, detection 515 nm), it is transmitted with time from the mucosal side to the basement membrane side (forward) and from the basement membrane side to the mucosa side (reverse direction) at 37 ° C. The amount of the fluorescent marker was measured using a fluorometer (spectra MAX GEM manufactured by Molecular Devices).
INI ”). FIG. 3 shows the permeation amount of the fluorescent marker FC over time, and FIG. 4 shows the permeation amount of the fluorescent marker LY over time.
Shown in 3 and 4, FC is permeated and absorbed from the mucosal side to the basement membrane side (forward direction≫reverse direction), whereas L
In Y, the permeation amount from the mucosa side to the basement membrane side and the permeation amount from the basement membrane side to the mucosa side were almost the same (forward direction ≒ reverse direction). Conventional knowledge has recognized that LY and FC are permeated and absorbed in the intercellular space (forward ≒ reverse) (Hash
imoto K. et al, BBB, 58, 1345, 1994, Sakai M. e
t al, J. Pharm. Sci., 86, 779, 1997, etc.), but FC has a positive polarity from the mucosal side to the basement membrane side depending on the H ⁺ gradient between the mucosal side and the basement membrane side. It became clear for the first time that it was transmitted.

Example 5 (Verification of FC Absorption Mechanism-Energy Dependence) HBSS buffer pH 7.4 was added to the basement membrane side well and HBSS buffer pH 6.0 was prepared to the mucosal side well. FC 40 μg / ml-5 mM NaN ₃ (respiratory inhibitor) was added, and the permeation amount of FC permeated from the mucosal side to the basement membrane side over time was measured in the same manner as in the above example. In addition, the permeation amount of FC permeated from the mucous membrane side to the basement membrane side over time at 4 ° C. instead of 37 ° C. was measured in the same manner as in the above-mentioned Example. FIG. 5 shows the results. From FIG. 5, since the amount of permeated FC decreases significantly due to the coexistence of a respiratory inhibitor and a decrease in temperature, it was inferred that FC is permeated depending on energy.

Example 6 (Verification of FC Absorption Mechanism-Consistency with Conventional Findings-) HBSS buffer pH 7.4 was added to the basement membrane side well, and the HBSS buffer pH 7.4 was added to the mucosal side well. (Additional direction) with 40 μg / ml of FC prepared in
7.4 / 7.4) and HBSS buffer p
H7.4 was added, and the basement membrane side well was simultaneously provided with an experimental section (reverse direction 7.4 / 7.4) to which 40 μg / ml of FC prepared with HBSS buffer pH 7.4 was added. The directionality regarding FC permeation absorption when no H ⁺ gradient was present between the membrane sides was verified. For comparison, HBSS buffer pH 7.4 was added to the basement membrane side well, and FC prepared with HBSS buffer pH 6.0 was added to the mucosal side well.
Experimental group to which 40 μg / ml was added (forward 6/7.
4) was also set, and the FC permeation and absorptivity in the presence of an H ⁺ gradient were compared. FIG. 6 shows the results. As is clear from FIG. 6, when there is no H ⁺ gradient, the amount of permeation from the mucosal side to the basement membrane side and the amount of permeation from the basement membrane side to the mucosal side are almost the same for FC as for LY. FC (forward ≒ reverse), but as with the actual intestinal absorption, if there is an H ⁺ gradient between the mucosal side and the basement membrane side, FC will first transfer energy from the mucosal side to the basement membrane side. Polar transport is dependent. In contrast, the polar transport was not observed in many previous cases which were examined at the mucosal side pH 7.4 / basement membrane side pH 7.4 (there is no H ⁺ gradient) in consideration of cell damage. It is estimated that

Example 7 (Verification of Absorption Mechanism of FC or LY-Localization-) It was inferred from Examples 3 to 6 that the absorption mechanism of FC and LY was different. Therefore, HBSS was added to the basement membrane side well. Buffer p
H7.4 was added, and HBSS buffer p was added to the mucosal side well.
FC 40 μg / ml prepared with H6.0 and LY400
After performing a permeation experiment in the same manner as in the above example by adding μg / ml, the mucosal fluid, the basement membrane fluid, and Caco-2 were added.
The cell disruption suspensions were individually collected, and the amount of the fluorescent marker remaining in each fraction was measured in the same manner as in the above example, and the localization of the remaining FC and LY was verified. FIG. 7 shows the results. As is clear from FIG.
While present on the basement membrane side and in the cell, respectively, L
In Y, almost all remained on the mucosal side, indicating that only a part of LY that had permeated the Caco-2 cell layer was present on the basement membrane side.

Example 8 (Verification of FC absorption mechanism-TE
R and permeation amount−) Since it was presumed that the absorption mechanism of FC and LY was different according to Examples 3 to 7, the absorption mechanism of FC was analyzed in more detail. Caco-2 monolayer cells of various TERs were prepared by treating Caco-2 monolayer cells prepared according to Example 1 with cytochalasin D (Kim M. et al, Bios).
ci. Biotechnol. Biochem., 63, 2183, 1999). Next, HBSS buffer pH 7.4 was added to the basement membrane side well, and FC40 ug / FC prepared with HBSS buffer pH 6.0 and HBSS buffer pH 7.4 was added to the mucosal side well.
of the fluorescent marker per unit area per unit time at 37 ° C. from the mucosal side to the basement membrane side (permeation amount; Flux / ng / min / cm ² ) in the same manner as in the above-mentioned Example. did. In [1] of FIG. 8 where the H ⁺ gradient exists, the TER
Whereas FC permeation amount is substantially constant without being influenced by, TER in [2] of FIG. 8 H ⁺ gradient is not present and F
An inverse correlation was observed in the amount of C transmission. That is, FC is absorbed into the intercellular space in the absence of the H ⁺ gradient (Hashimoto K. et al, Biosci. Biotechnol. Bioch.
em., 58, 1345, 1994), which was shown to be absorbed mainly intracellularly in the presence of an H ⁺ gradient.

Example 9 (Validation of FC Absorption Mechanism-Substrate Concentration and Initial Permeation Rate-) In order to examine whether a specific receptor is involved in the absorption mechanism of FC, the wells on the basement membrane side were examined. Contains HBSS buffer p
H7.4 was added, and HBSS buffer p was added to the mucosal side well.
Various concentrations of FC prepared with H6.0 or HBSS buffer pH 7.4 were added (10 ug / ml to 4 mg / ml), and the amount of FC permeated from the mucosal side to the basement membrane side over time was determined as described above. Measurement was performed in the same manner as in the example, and the FC permeation initial velocity was calculated from the initial permeation time at which linear regression was possible (Tsuji A. et al, Pharm.
Res., 11, 30, 1994), [1] in FIG. 9, and [2] in FIG.
Shows the results. [1] in FIG. 9 where an H ⁺ gradient exists
As the FC concentration increased, the increase in the initial FC permeation rate gradually decreased, and a saturation-like curve (Michaelis Menten-type saturation curve + simple diffusion) was observed. That is, it suggests that FC is specially transported via a receptor in addition to simple diffusion transport. On the other hand, in [2] of FIG. 9 where there is no H ⁺ gradient, the initial FC permeation rate increases linearly with an increase in the FC concentration, suggesting that simple diffusion transport is performed.

Example 10 (Verification of FC Absorption Mechanism -Effect of Inhibitor and Substrate-) HBSS buffer pH 7.4 was added to the basement membrane side well, and HBSS buffer pH 6.0 was added to the mucosal side well. After adding 40 ug / ml of the FC prepared in the above, and adding various concentrations of the transport substrate and the inhibitor prepared in the HBSS buffer pH 6.0 to the mucosal side well (70 uM to 12.5 mM) and coexisting with the FC, The initial FC permeation rate was calculated in the same manner as in the Example. In addition, FIG. 10 shows the results of the relative initial permeation rate of each test sample when the FC permeation initial velocity of the control was set to 100%, with the control to which HBSS buffer pH 6.0 was added in place of the inhibitor and the substrate. It was shown to. As is clear from FIG. 10, Gly-Sar which is a typical substrate of the peptide transporter, A which is an endocytosis inhibitor
Mantadine, Brefeidine A, and DIDS which is an anion antiporter inhibitor (Sai Y.
et al, Pharm. Res., 15, 1305, 1998; Ogihara T. et
al, J. Pharm. Sci., 88, 1217, 1999) FC is a peptide expressed in the intestinal epithelium because it is specifically inhibited only by the energy inhibitor NaN ₃ without being inhibited at all. It was speculated that it was absorbed via transporters, anion antiporters, or other energy-dependent receptors that were not endocytosis (Tsuji A. et al, Pharm. Res., 13,963, 1996).

Example 11 (Verification of FC absorption mechanism -M
Effect of CT Substrate-) HBSS buffer pH 7.4 was added to the basement membrane side well, FC40 ug / ml prepared with HBSS buffer pH 6.0 was added to the mucosal side well, and HBSS buffer pH 6.0 was further added. Add various MCT (monocarboxylic acid transporter) substrates prepared in the above to the mucosal side well (10 mM)
After coexisting with FC, the initial FC permeation velocity was calculated in the same manner as in the above-described example, and the result of the relative initial permeation velocity was shown in FIG. As is clear from FIG. 11, acetic acid, propionic acid,
MCT of butyric acid, salicylic acid, benzene acid, valproic acid, etc.
Substrate (Hiroaki Yuasa et al., History of Medicine, 197, 3, 2001) significantly inhibits the initial FC permeation rate.
Was first shown to be absorbed by MCTs. Although the following structure of FC (formula [I]) and structure of LY (formula [II]) are shown, it is presumed that MCT is absorbed by recognizing a free carboxyl group of FC.

[0045]

Embedded image

Example 12 (Screening of absorption promoting substance using LY or FC) A fluorescent marker prepared with HBSS buffer pH 6.0 and each test sample were added to a mucosal well of a Caco-2 cell layer. Each of the fluorescent markers has a concentration of 400
μg / ml lucifer yellow (LY: excitation 430n
m, detection 535 nm) or 40 μg / ml sodium fluorescein (FC: excitation 492 nm, detection 515 n)
m) was used. Each test sample had a final concentration of 5 mg /
ml. Amount of fluorescent marker permeating per unit area from mucosal side to basement membrane side at 37 ° C. per unit time (permeation amount: Flux / ng / min / c
m ² ) with a fluorometer (Molecular Devices “spectra
MAX GEMINI "). A control to which HBSS buffer pH 6.0 was added instead of the test sample was used as a control. When measuring, the osmotic pressure and pH on the mucosal side are
It was also confirmed that there was almost no difference between the samples. FIG. 12 (see [1] and [2]) shows the result of the transmission amount of the fluorescent marker LY, and FIG. 13 shows the result of the transmission amount of the fluorescent marker FC. As can be seen from FIG. 12, spinach, galangal, myoga, chive, marigold, jasmine,
Extracts from meguri trees, oakhiji, whitebait, hops and cordyceps significantly promoted the absorption of LY, but the extract of shishido did not show much LY absorption promoting activity. As can be seen from FIG. 13, it was found that extracts from black pepper, cardamom, and black tea significantly promoted FC absorption.

Example 13 (Concentration Dependence of Absorption-Promoting Activity) Spinach, galangal, myogyo, marigold, jasmine, which had LY absorption-promoting activity in Example 12,
Concentration-dependent effects were examined for extracts from meguri trees, okajiki, whitebait, hops, cordyceps, and black pepper, cardamom, and black tea, each of which had an FC absorption promoting activity. Spinach, galangal, myogyo, marigold,
Each extract of Jasmine, Megusuri tree, Okahiji, whitebait, hops, Cordyceps, black pepper and cardamom was added to the mucosa side to a final concentration of 0.5 to 5 mg / ml,
The transmission amount of the LY fluorescent marker or the transmission amount of the FC fluorescent marker was measured in the same manner as in Example 12. The results are shown in FIGS. 14 to 26, respectively. From FIG. 14 to FIG. 26, it can be seen that the absorption promoting activity of each of the above extracts increases depending on the added concentration.

Example 14 (Calcium absorption promoting effect) Calcium was selected and used as a preferred functional component for the human body instead of a fluorescent marker. Each extract of galangal, marigold, meguri tree, whitebait, hops, and shishitsu as a negative control, for which the LY absorption promoting effect was recognized in Example 12, was added (5 mg / ml), and the extract was replaced with a fluorescent marker. Example 12 except that calcium chloride having a final concentration of 10 mM dissolved in HBSS buffer pH 6.0 was used.
Similarly, the amount of calcium (Flux ng / min / cm ² ) that permeates from the mucosal side to the basement membrane side is calculated as calcium E
It was measured using Test Wako (manufactured by Wako Pure Chemical Industries). The results are shown in FIG. As shown in FIG. 27, extracts from galangal, marigold, megsuri tree, sardines, and hops significantly enhance calcium absorption, while succulent extracts significantly enhance calcium absorption. Did not.

Example 15 (Absorption-promoting effect of oligopeptides) Oligopeptides (Gln-Gln-Gln-Pro-Pr
o) was selected. This oligopeptide is the major epitope structure of wheat allergen (Tanabe S., BBR
C., 219, 290, 1996), which itself is expected to exhibit an anti-allergic effect because it does not cause an allergic reaction such as histamine release and antagonistically inhibits the binding between allergen and IgE (Tanabe) Soichi, History of Medicine, 18
3,866,1997). Therefore, the respective extracts of spinach, galangal, myogyo, marigold, jasmine, megusuri tree, oakhijiki, whitebait, hops, and shishitsu as a negative control, which were confirmed to have the LY absorption promoting effect in Example 12, were added (5 mg / g). ml), and the FI dissolved in HBSS buffer pH 6.0 was used instead of the fluorescent marker.
TC-labeled oligopeptide Gln-Gln-Gl
n-Pro-Pro (manufactured by Peptide Institute) has a final concentration of 1
The amount of peptide (Flux ng / min / cm ² ) permeating from the mucosal side to the basement membrane side was measured in the same manner as in Example 12 except that the amount was added so that the concentration became 00 to 500 μg / ml. 515 nm).
The results are shown in FIG. As shown in FIG. 28, the extracts from spinach, galangal, myogyo, marigold, jasmine, megsuri tree, okahiji, shirasu, and hops significantly enhance peptide uptake.
The sugar extract did not significantly enhance peptide absorption.

Example 16 (Flavonoid Absorption Enhancing Effect) Quercitrin (flavonoids) was selected as a preferred functional component for the human body instead of a fluorescent marker. Example 12
Each extract of marigold, jasmine, megsuri tree, oakhijiki, and whitebait, for which the LY absorption promoting effect was recognized, was added (5 mg / ml), and instead of the fluorescent marker,
200 μM final concentration dissolved in HBSS buffer pH 6.0
Was used to measure the amount of quercitrin that permeated from the mucosal side to the basement membrane side. The measurement of quercitrin amount is
After the total amount of the permeated solution on the basement membrane side is concentrated by lyophilization, HPLC analysis [column: LiChrospher 100 RP-18
(Manufactured by Kanto Chemical Co., Ltd.), flow rate: 1.0 ml / min, mobile phase: solution A; 5% N, N-dimethylformaldehyde-
0.1% acetonitrile-0.1% phosphoric acid solution, solution B;
Two-part gradient elution of acetonitrile, column temperature:
40 ° C., detection: 380 nm, injection volume: 50 μl]. FIG. 29 shows the results of the rate of increase / decrease in the amount of quercitrin permeated in each sample-added section relative to the control section (HBSS buffer pH 6.0-added section). As shown in FIG. 29, the extracts of marigold, jasmine, megsuri tree, okajiki and whitebait, especially the extract of megsuri tree, significantly promoted the absorption of quercitrin.

Example 17 (Effect of Promoting Absorption of Flavonoids) Caco-2 cells in which naringin (flavonoids) was selected as a functional component to be taken orally instead of a fluorescent marker and 2 mM naringin / HBSS buffer pH 6.0 was added Then, the extract from spinach, galangal, myoga, marigold, jasmine, megsuri tree, oakhijiki, and hops, which was confirmed to have the LY absorption promoting effect in Example 12, was added (5 mg / ml) for a certain period of time. The amount of naringin permeated to the basement membrane side per area was measured. The measurement was performed by HPLC analysis of the permeated basement membrane side solution [column: Li
Chrospher 100 RP-18 (manufactured by Kanto Chemical Co.), flow rate: 1.0
ml / min, mobile phase: water: acetonitrile: THF:
Acetic acid = 80: 16: 3: 1, column temperature: 40 ° C., detection: 280 nm, injection volume: 50 μl],
FIG. 30 shows the results of the rate of increase and decrease in the amount of permeation of naringin in each sample-added section relative to the control (HBSS buffer pH 6.0-added section). As shown in FIG. 30, the extract significantly promoted the absorption of naringin.

Example 18 (Cytotoxicity due to LDH release rate) DMEM (Dulbecco's modified Eagle medium) according to a standard method
The medium was removed from the plate of Caco-2 cells cultured in a 24-well plate (Falcon) using
After washing several times with ml of HBSS buffer pH 6.0,
Spinach, galangal, myoga as test sample,
0.4 ml of each extract (5 mg / ml HBSS buffer pH 6.0) of Chinese chive, marigold, jasmine, meguri tree, okajiki, shirasu, hop, black pepper, cardamom, black tea, and cordyceps was added. The LDH (lactate dehydrogenase) in the supernatant after the reaction was converted into free LDH, and the LDH in the extract obtained by ultrasonically crushing the cells was converted into intracellular LH.
As free DH, these free LDH and intracellular LDH are referred to as LDH.
(Lactate dehydrogenase) —measured using a cytotoxicity test Wako (manufactured by Wako Pure Chemical Industries, Ltd.), and the LDH release rate% (= free LDH)
/ (Free LDH + intracellular LDH) × 100), the cytotoxicity of the test sample was verified. The sample to which HBSS buffer pH 6.0 was added instead of the test sample was used as a control, and saponin (0.1 to 1 mg) causing cell membrane damage was used as a control.
/ Ml HBSS buffer (pH 6.0) was used as a positive control (Narai A et al, Toxicology in Vitro, 1).
1,347,1997). The results are shown in FIG. From FIG. 31, free LDH increased as the added concentration of saponin increased, confirming the cytotoxicity of saponin. On the other hand,
The LDH release rate of the test sample was equal to or lower than that of the control, indicating that the test sample had almost no cytotoxicity.

Example 19 (Cytotoxicity due to respiratory inhibition rate) DMEM (Dulbecco's modified Eagle's medium) according to a standard method
The medium was removed from the plate of Caco-2 cells cultured in a 24-well plate (Falcon) using
After washing several times with ml of HBSS buffer pH 6.0,
Spinach, galangal, myoga as test sample,
0.4 ml of each extract (5 mg / ml HBSS buffer pH 6.0) of Chinese chive, marigold, jasmine, megsuri tree, oakhijiki, shirasu, hop, black pepper, cardamom, black tea, cordyceps, After the reaction, 0.4 ml of Alamar Blue test solution (manufactured by Iwaki Glass Co., Ltd.) was added, and the fluorescence intensity (excitation: 560 nm, detection: 590 n)
m) was measured to verify the respiratory inhibition rate. As a control, a saponin (0. 0, 1) which causes cell membrane damage was used as a control, in which HBSS buffer pH 6.0 was added instead of the test sample.
The addition of 1 to 1 mg / ml HBSS buffer (pH 6.0) was used as a positive control. The results are shown in FIG. FIG.
From this, it was confirmed that when the added concentration of saponin was increased, the respiratory inhibition rate was increased, and the cytotoxicity of saponin could be confirmed. On the other hand, the respiratory inhibition rate of the test sample was very low, indicating that there was almost no cytotoxicity.

Example 20 (Screening of absorption promoting substance using RH) A fluorescent marker prepared with HBSS buffer solution pH 6.0 and each test sample were added to the well on the mucosal side of the Caco-2 cell layer. As a fluorescent marker, a concentration of 100 μg / m
l of rhodamine (RH: excitation 505 nm, detection 540 n
m) was used. Each test sample had a final concentration of 5 mg /
ml. Amount of fluorescent marker permeated per unit area per unit area from mucosa side to basement membrane side at 37 ° C. for 90 minutes (permeation amount: Flux / ng / mi)
n / cm ² ) with a fluorometer (Molecular Devices “sp”
ectra MAX GEMINI ”). A control to which HBSS buffer pH 6.0 was added instead of the test sample was used as a control. In the measurement, the osmotic pressure and p
H also confirmed that there was almost no difference between the samples. The results are shown in FIG. As can be seen from FIG. 33, the extract of Hechima significantly promoted the absorption of RH, but other extracts such as Chinese cabbage did not show the activity of promoting the absorption of RH.

Example 21 (Concentration Dependence of Absorption-Promoting Activity) The concentration-dependent effect of the extract of Hemba, in which the RH absorption-promoting activity was observed in Example 20, was examined. Hechima extract was added to the mucosa side to a final concentration of 0.5 to 5 mg / ml, and the amount of permeation of the RH fluorescent marker was measured in the same manner as in Example 20. The results are shown in FIG. FIG.
From the results, it can be understood that the activity of promoting the absorption of the Hichima extract increases depending on the added concentration.

Example 22 (Cytotoxicity due to LDH release rate) DMEM (Dulbecco's modified Eagle medium) according to a standard method
The medium was removed from the plate of Caco-2 cells cultured in a 24-well plate (Falcon) using
After washing several times with ml of HBSS buffer pH 6.0,
Hichima extract (5 mg / ml HB
0.4 ml of SS buffer (pH 6.0) was added. The LDH (lactate dehydrogenase) in the supernatant after the reaction was converted into free LDH, and the LDH in the extract obtained by ultrasonically crushing the cells was converted into intracellular LH.
As free DH, these free LDH and intracellular LDH are referred to as LDH.
(Lactate dehydrogenase) —measured using a cytotoxicity test Wako (manufactured by Wako Pure Chemical Industries, Ltd.), and the LDH release rate% (= free LDH)
/ (Free LDH + intracellular LDH) × 100), the cytotoxicity of the test sample was verified. The sample to which HBSS buffer pH 6.0 was added instead of the test sample was used as a control, and saponin (0.1 to 1 mg) causing cell membrane damage was used as a control.
/ Ml HBSS buffer (pH 6.0) was used as a positive control (Narai A et al, Toxicology in Vitro, 1).
1,347,1997). The results are shown in FIG. From FIG. 35, when the added concentration of saponin was increased, free LDH was increased, and the cytotoxicity of saponin could be confirmed. On the other hand,
The LDH release rate of the test sample was equal to or lower than that of the control, indicating that the test sample had almost no cytotoxicity.

Example 23 (Cytotoxicity due to respiratory inhibition rate) DMEM (Dulbecco's modified Eagle medium) according to a standard method
The medium was removed from the plate of Caco-2 cells cultured in a 24-well plate (Falcon) using
After washing several times with ml of HBSS buffer pH 6.0,
Hichima extract (5 mg / ml HB
0.4 ml of SS buffer (pH 6.0) was added and reacted. After the reaction, 0.4 ml of Alamar Blue test solution (manufactured by Iwaki Glass Co., Ltd.) was added and the fluorescence intensity (excitation 560 nm, detection 590 nm) was measured to verify the respiratory inhibition rate. In addition,
A saponin (0.1 to 1 mg / ml HBSS buffer pH 6.0) that causes cell membrane damage is used as a control, in which HBSS buffer pH 6.0 is added instead of the test sample.
Was used as a positive control. The results are shown in FIG. From FIG. 36, the respiratory inhibition rate increased when the added concentration of saponin was increased, and the cytotoxicity of saponin could be confirmed. On the other hand, the respiratory inhibition rate of the test sample was very low, indicating that there was almost no cytotoxicity.

[0058] The tablet with improved absorption of calcium and vitamin D ₃ in the formulations shown in Table 1 of Example 24 (Food and admixing an absorption enhancer) will increase the calcium absorption promotion effect to the formulation shown in Table 2 Yogurt jelly, a cookie with an enhanced polyphenol absorption promoting effect with the composition shown in Table 3, a nutritional beverage with an enhanced calcium and polyphenol absorption enhancing effect with the composition shown in Table 4, and a polyphenol with the composition shown in Table 5 Tablets having an enhanced absorption-promoting effect, juices having an increased absorption of β-carotene in the composition shown in Table 6, and capsules having an enhanced absorption of the active ingredient in wheat germ oil having the composition shown in Table 7 were obtained by a conventional method. Manufactured by According to a conventional method, capsules having the absorption of butyric acid useful as an energy source for the intestinal tract with the composition shown in Table 8 below were used, and ferulic acid, coumaric acid, gallic acid, A mixed tea with enhanced absorption of polyphenol compounds such as catechins was produced.

[0059]

[Table 1]

[0060]

[Table 2]

[0061]

[Table 3]

[0062]

[Table 4]

[0063]

[Table 5]

[0064]

[Table 6]

[0065]

[Table 7]

[0066]

[Table 8]

[0067]

[Table 9]

[0068]

EFFECT OF THE INVENTION The use of the total absorption enhancer or absorption enhancer of the present invention effectively promotes the absorption of useful functional components in foods and drinks, or the effective components of orally administered drugs, and improves the in vivo utilization rate. Can be significantly improved, and the effects in foods and drinks can be exhibited more effectively by ingesting them in combination with healthy foods and drinks and functional foods and drinks that are conscious of physiological effects.

[Brief description of the drawings]

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a view showing the results (fluorescent marker; sodium fluorescein) of the effect of mucosal pH on the absorption mechanism of the intestinal absorption model used in the present invention.

FIG. 2 is a view showing the results of examining the effect of pH on the mucosa side in the absorption mechanism of the intestinal absorption model used in the present invention (fluorescent marker; Lucifer Yellow).

FIG. 3 is a graph showing the results of examination on the transmission directionality in the absorption mechanism of the intestinal absorption model used in the present invention (fluorescent marker; sodium fluorescein). In the figure, μ indicates μg / ml (the same applies hereinafter).

FIG. 4 is a diagram showing the results of a study on the transmission directionality in the absorption mechanism of the intestinal absorption model used in the present invention (fluorescent marker; Lucifer Yellow).

FIG. 5 is a graph showing the results of investigating the energy dependence of the intestinal absorption model used in the present invention in the absorption mechanism (fluorescent marker; sodium fluorescein).

FIG. 6 is a graph showing the results of investigating the effect of an H ⁺ gradient on the absorption mechanism of the intestinal absorption model used in the present invention (fluorescent marker; sodium fluorescein).

FIG. 7 is a diagram showing the results of examining the localization of fluorescent markers (sodium fluorescein and lucifer yellow) in the absorption mechanism of the intestinal absorption model used in the present invention.

FIG. 8 is a diagram showing the results of measuring the relationship between the amount (permeation amount) of a fluorescent marker and TER for analyzing FC absorption mechanism in the present invention.

FIG. 9 is a diagram showing the results of measuring the relationship between the FC concentration and the initial FC permeation rate for analyzing the FC absorption mechanism in the present invention.

FIG. 10 is a diagram showing the results of measuring the relative initial permeation rate of each test sample (inhibitor, substrate of each transport system) for analyzing FC absorption mechanism in the present invention.

FIG. 11 is a diagram showing the results of measuring the relative initial velocity of each test sample (MCT substrate) for analyzing FC absorption mechanism in the present invention.

FIG. 12 is a view showing the results of screening (fluorescent marker; Lucifer Yellow) of the absorption promoter of the present invention.

FIG. 13 is a view showing the results of screening (fluorescent marker; sodium fluorescein) of the absorption promoter of the present invention.

FIG. 14 is a diagram showing the absorption promoting effect of the absorption enhancer spinach extract of the present invention. In the figure, m indicates mg / ml (the same applies hereinafter).

FIG. 15 is a graph showing the absorption promoting effect of the absorption enhancer galangal extract of the present invention.

FIG. 16 is a graph showing the absorption promoting effect of the absorption enhancer Myoga extract of the present invention.

FIG. 17 is a view showing the absorption promoting effect of the absorption enhancer marigold extract of the present invention.

FIG. 18 is a graph showing the absorption promoting effect of the absorption enhancer jasmine extract of the present invention.

FIG. 19 is a graph showing the absorption promoting effect of the tree extract of the absorption promoter of the present invention.

FIG. 20 is a graph showing the absorption promoting effect of the absorption enhancer Okahijiki extract of the present invention.

FIG. 21 is a graph showing the absorption-promoting effect of the absorption promoter Shirasu extract of the present invention.

FIG. 22 is a graph showing the absorption promoting effect of the absorption enhancer hop extract of the present invention.

FIG. 23 is a graph showing the absorption promoting effect of the black pepper extract of the present invention.

FIG. 24 is a view showing the absorption promoting effect of the cardamom extract of the present invention.

FIG. 25 is a graph showing the absorption promoting effect of the absorption promoter black tea extract of the present invention.

FIG. 26 is a graph showing the absorption promoting effect of the absorption promoter of the present invention.

FIG. 27 is a graph showing the effect of promoting absorption of calcium by the absorption promoter of the present invention.

FIG. 28 is a graph showing the effect of promoting absorption of an oligopeptide by the absorption promoter of the present invention.

FIG. 29 is a graph showing the effect of promoting absorption of quercitrin by the absorption promoter of the present invention.

FIG. 30 shows the effect of promoting absorption of naringin by the absorption promoter of the present invention.

FIG. 31 is a view showing the results of examining the cytotoxicity of the absorption enhancer of the present invention based on the release rate of LDH (lactate dehydrogenase).

FIG. 32 is a view showing the results of examining the cytotoxicity of the absorption enhancer of the present invention based on the respiratory inhibition rate.

FIG. 33 shows the results of screening for the absorption promoter of the present invention.

FIG. 34 is a graph showing the absorption promoting effect of the absorption enhancer extract of the present invention.

FIG. 35 is a graph showing the results of examining the cytotoxicity of the absorption enhancer of the present invention based on the release rate of LDH (lactate dehydrogenase).

FIG. 36 is a view showing the results of verifying the cytotoxicity of the absorption enhancer of the present invention by the respiratory inhibition rate.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 47/46 A61K 47/46 4C084 A61P 3/02 A61P 3/02 7/02 7/02 17/16 17 / 16 35/00 35/00 37/04 37/04 39/06 39/06 C12Q 1/02 C12Q 1/02 G01N 21/78 G01N 21/78 C 33/15 33/15 Z (72) Inventor Hagiwara Keiko 3 Miyagawa-cho, Takasaki City, Gunma Prefecture Kirin Brewery Co., Ltd. Application Development Center F term (reference) 2G045 BB20 BB51 CB01 CB20 FA26 FB12 GC15 2G054 AA06 CE02 EA03 EB01 GA03 4B018 LB01 LB08 LB10 LE01 LE02 MD05 MD23 MD23 MD23 MD48 MD23 MD48 MD74 4B063 QA05 QQ02 QQ04 QQ08 QQ61 QQ91 QR41 QR77 QS24 QS36 QX02 QX04 4C076 AA06 AA11 AA17 AA22 AA29 AA37 AA49 AA53 BB01 CC07 CC18 CC21 CC27 EE57N EE58N FF34 4C084 AA37 MA17 MAA23 MAA MAA 3 MA52 NA07 NA11 ZA892 ZB092 ZB262 ZC222 ZC752

Claims (25)

[Claims] The present invention relates to Caco-2 cells derived from human colon cancer.
Cultured on a transient membrane, morphologically and functionally intestinal-like monolayer
Cell layer, pH 6.0 buffer solution on the mucosal side, basal
A buffer solution of pH 7.4 is added to the membrane side to absorb the intestinal tract of the living body.
H same as time ⁺After forming a gradient and equilibrating, Cac
Measure transepithelial electrical resistance (TER) of o-2 monolayer cells
It is determined that a sufficient tight junction has been formed.
Cells to be cut off (TER ≧ 200Ω · cm^Two)
Prepared Caco-2 cells were prepared with pH 6.0 buffer
Multiple fluorescent markers with different absorption mechanisms manufactured individually
And a test substance prepared in the same manner with a buffer solution of pH 6.0.
Add to the mucous membrane side and penetrate from the mucosal side to the basement membrane side
Time and amount of fluorescent marker per fixed area
To measure individually at the appropriate wavelength for each fluorescent marker
Separation of absorption promoters with different absorption mechanisms
Screening method. 2. A method according to claim 1, wherein two or three fluorescent markers selected from lucifer yellow (LY), sodium fluorescein (FC) and rhodamine (RH) are used as the plurality of fluorescent markers having different absorption mechanisms. 2. The method for individually screening for absorption promoting substances having different absorption mechanisms according to claim 1. 3. Caco-2 cells derived from human colon cancer are passed through
Cultured on a transient membrane, morphologically and functionally intestinal-like monolayer
Cell layer, pH 6.0 buffer solution on the mucosal side, basal
A buffer solution of pH 7.4 is added to the membrane side to absorb the intestinal tract of the living body.
H same as time ⁺After forming a gradient and equilibrating, Cac
Measure transepithelial electrical resistance (TER) of o-2 monolayer cells
It is determined that a sufficient tight junction has been formed.
Cells to be cut off (TER ≧ 200Ω · cm^Two)
Prepared Caco-2 cells were prepared with pH 6.0 buffer
Fluorescent marker made of sodium fluorescein
And a test substance prepared with a buffer solution of pH 6.0.
When added to the membrane side and permeates from the mucosal side to the basement membrane side
The amount of fluorescent marker per fixed area
Screening of absorption-promoting substances characterized by measurement
Method. 4. The screening method according to claim 1, wherein the absorption promoting substance has substantially no cytotoxicity. 5. A combination of absorption promoting substances having different absorption mechanisms obtained by the screening method using a plurality of fluorescent markers having different absorption mechanisms according to claim 1 or 2 as an active ingredient. And a comprehensive absorption enhancer. 6. A combination of absorption promoting substances having different absorption mechanisms can be obtained by a LY absorption promoting substance group obtained by a screening method using lucifer yellow as a fluorescent marker and a screening method using sodium fluorescein as a fluorescent marker. It is a combination of a FC absorption promoting substance group and two or three or more absorption promoting substances having different absorption mechanisms selected from the RH absorption promoting substance group obtained by a screening method using rhodamine as a fluorescent marker. The total absorption enhancer according to claim 5, wherein 7. The LY absorption promoting substance group includes spinach, galangal, myogyo, chive, marigold, jasmine, megusuri tree, okajiki, whitebait, hop, cordyceps,
Or selected from these processed products, wherein the FC absorption-promoting substance group is selected from black pepper, cardamom, black tea or these processed products, and the RH absorption-promoting substance group is selected from henchma or processed products thereof. The total absorption enhancer according to claim 6. 8. The total absorption enhancer according to claim 7, wherein the processed product is an extract. 9. An absorption enhancer obtained by a screening method using sodium fluorescein as the fluorescent marker according to claim 3 or 4. 10. An active ingredient containing one or more selected from spinach, galangal, myoga, chive, marigold, jasmine, meguri tree, oakhiji, whitebait, hop, cordyceps, or a processed product thereof. An absorption enhancer characterized in that: 11. An absorption enhancer comprising, as an active ingredient, one or two selected from black pepper, cardamom, black tea or a processed product thereof. 12. An absorption enhancer comprising a henchma or a processed product thereof as an active ingredient. 13. The absorption enhancer according to claim 10, wherein the processed product is an extract. 14. A method for promoting the absorption of orally ingested functional components, characterized in that the total absorption enhancer according to any one of claims 5 to 8 is added to and blended with a food or beverage containing a preferred functional component. Food and drink that can. 15. The promotion of absorption of an orally ingested functional component according to claim 14, wherein the total absorption enhancer is added and blended in an amount of 0.2 to 30% by weight as a solid content in the extract. Food and drink that can be. 16. A food or drink capable of promoting the absorption of orally ingested functional components, wherein the absorption enhancer according to claim 10 or 13 is added to or blended with a food or drink containing a preferred functional component. Goods. 17. The method according to claim 9, wherein the absorption enhancer according to claim 9, 11 or 13 is added to or blended with a food or drink containing a preferred functional component, thereby facilitating the absorption of the orally ingested functional component. Food and drink that can be. 18. A food or drink capable of promoting the absorption of orally ingested functional components, wherein the absorption enhancer according to claim 12 or 13 is added to or blended with a food or drink containing a preferred functional component. Goods. 19. The orally ingested functional ingredient according to claim 16, wherein the absorption enhancer is added and blended in an amount of 0.2 to 30% by weight as a solid content in the extract. Foods and drinks that can promote the absorption of water. 20. The method according to claim 14, wherein the preferred functional component is one or more components selected from minerals, monocarboxylic acids, flavonoids, vitamins, polyphenols, and carotenoids. 20. A food or drink which is capable of promoting the absorption of the orally ingested functional ingredient according to any one of the above items 19. 21. A method for promoting the absorption of orally ingested functional components, characterized in that the total absorption enhancer according to any one of claims 5 to 8 is added to and blended with a drug containing a preferred functional component. Drugs that can be. 22. A medicament capable of promoting the absorption of orally ingested functional components, characterized in that the absorption enhancer according to claim 10 or 13 is added or blended with a medicament containing a preferred functional component. 23. The absorption enhancer according to claim 9, 11 or 13 is added to or blended with a drug containing a preferred functional ingredient, thereby facilitating the absorption of an orally ingested functional ingredient. Pharmaceuticals. 24. A medicament capable of promoting the absorption of orally ingested functional components, characterized in that the absorption enhancer according to claim 12 or 13 is added to and blended with a medicament containing preferred functional components. 25. The method according to claim 21, wherein the preferred functional component is one or more components selected from minerals, monocarboxylic acids, flavonoids, vitamins, polyphenols, and carotenoids. 24. A medicament capable of promoting absorption of a functional ingredient taken orally according to any one of 24.