WO2016104524A1

WO2016104524A1 - Agent for enhancing adherens junction function

Info

Publication number: WO2016104524A1
Application number: PCT/JP2015/085867
Authority: WO
Inventors: 眞里柚鳥
Original assignee: ライオン株式会社
Priority date: 2014-12-24
Filing date: 2015-12-22
Publication date: 2016-06-30
Also published as: MY186939A; JPWO2016104524A1; JP6755185B2; KR20170097013A; CN107106539A; CN111658640A

Abstract

Provided are an agent for enhancing adherens junction functions, an agent for enhancing E-cadherin, an agent for strengthening intracellular binding force, an agent for enhancing epithelial barrier functions and an agent for enhancing resistance, said agents each comprising at least one substance selected from the group consisting of phosphate esters of ascorbic acid and salts thereof, vitamin E and derivatives thereof, copper chlorophylls and salts thereof, and lysozyme chloride.

Description

Adhesion Junction Strengthening Agent

The present invention relates to an adhesion junction function enhancer, an E-cadherin enhancer, an intercellular binding force enhancer, an epithelial barrier function enhancer, and a resistance enhancer.

The epithelium is a cell layer covering the inner and outer surfaces of the body, such as the skin epidermis, nasal cavity, respiratory tract, oral cavity, digestive tract, and urogenital mucosa. The epithelium is equipped with a barrier function that prevents transpiration of water, damages caused by chemical and physical stimuli from the outside, and prevents pathogenic microorganisms from entering the body. Plays. It is known that the epithelial barrier function is reduced by stress, ultraviolet rays, temperature, humidity, infectious microorganisms, etc., and the reduction of the epithelial barrier function leads to the development of various disorders. For this reason, in the skin epidermis, an attempt has been made to use a skin external preparation containing a skin barrier function improving agent for the purpose of keeping the skin condition healthy (see Patent Document 1). The same applies to the mucous membrane, and maintaining the intestinal mucosal barrier function is known to be important for preventing and / or improving the development of insulin resistance and enteritis due to obesity. Attempts have been made to develop agents (see Patent Document 2).

It is known that the epithelial barrier function is formed by the connection between physical epithelial cells. This intercellular bond is formed by a cell adhesion device called tight junction, adherence junction (hereinafter also referred to as “AJ”), or gap junction. Among them, AJ plays a key role in a cell adhesion device, and it is known that the formation of AJ is indispensable for the formation of other cell adhesion devices (see Non-Patent Documents 1, 2, and 3).

About 20 types of cadherins are currently known as a family, but E (epithelial type) -cadherin is known as a cadherin species present in the skin epidermis, and E-cadherin is similarly expressed in human epithelial tissues. (See Non-Patent Document 4).

E-cadherin is a major component of AJ that plays an important role in maintaining epithelial barrier function, and is associated with epithelial barrier function failure (reflux esophagitis, inflammatory bowel disease, allergic rhinitis, stomatitis, teeth E-cadherin decreased expression is reported and suggested in peri-disease, dry mouth, bad breath, etc., and controlling the expression of E-cadherin in the epithelium is important for disease prevention and / or treatment. For example, Patent Document 1 focuses on E-cadherin, which is an epithelial cadherin, and promotes the expression of E-cadherin in human skin to improve skin wrinkles, sagging, and texture structure. Is described.

JP 2007-001914 A JP 2011-178864 A

The epithelium is a tissue that separates the inside and outside of the living body and has a physical barrier function against the transpiration of water and ions, which are important for maintaining the living body, and the invasion of pathogenic microorganisms. It has been. Such a decrease in barrier function is considered to cause various diseases. Thus, there is a potential need to provide new agents that enhance the epithelial barrier function.
An object of the present invention is to provide an agent that enhances the epithelial barrier function.

The present invention has been made in view of the above, wherein ascorbic acid phosphate and its salt, vitamin E and its derivative, copper chlorophyll and its salt, and lysozyme chloride enhance the expression of E-cadherin. Thus, the present invention has been completed by finding that it has an action of reinforcing the epithelial barrier function.

The present invention provides the following [1] to [21].
[1] An adherence junction function-enhancing agent containing at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
[2] The reinforcing agent according to [1], which is for mucosal epithelium.
[3] The reinforcing agent according to [1], which is for oral mucosal epithelium.
[4] The reinforcing agent according to [1], which is for gingival mucosal epithelium.
[5] An E-cadherin fortifier comprising at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
[6] The reinforcing agent according to [5], which is for mucosal epithelium.
[7] The reinforcing agent according to [5], which is for oral mucosal epithelium.
[8] The reinforcing agent according to [5], which is for gingival mucosal epithelium.
[9] An intercellular binding strength enhancer comprising at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
[10] The reinforcing agent according to [9], which is for mucosal epithelium.
[11] The reinforcing agent according to [9], which is for oral mucosal epithelium.
[12] The reinforcing agent according to [9], which is for gingival mucosal epithelium.
[13] An epithelial barrier function-enhancing agent comprising at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
[14] The reinforcing agent according to [13], which is for mucosal epithelium.
[15] The reinforcing agent according to [13], which is for oral mucosal epithelium.
[16] The reinforcing agent according to [13], which is for gingival mucosal epithelium.
[17] A resistance enhancer comprising at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
[18] The reinforcing agent according to [17], which is for mucosal epithelium.
[19] The reinforcing agent according to [17], which is for oral mucosal epithelium.
[20] The reinforcing agent according to [17], which is for gingival mucosal epithelium.
[21] The composition according to any one of [1] to [20], further comprising one or more selected from menthone, carvone, cineol, limonene, anethole, eugenol, menthol, and cinnamic aldehyde Strengthening agent.

According to the present invention, the epithelial barrier function can be effectively enhanced.

The agent of the present invention is at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride (hereinafter referred to as “component (A)”). Containing.

<Ascorbic acid phosphate and its salt>
Examples of the ascorbic acid phosphate ester include those in which the hydroxy groups at the 2nd, 3rd, 5th and 6th positions of ascorbic acid are esterified with phosphoric acid. The esterification site | part of ascorbic acid should just be 1 or more chosen from said each hydroxy group.

The phosphoric acid in the ascorbic acid phosphate ester is not particularly limited. For example, phosphoric acid; a monoalkyl ester of phosphoric acid (for example, one hydrogen contained in phosphoric acid is a methyl group, an ethyl group, a propyl group) Phosphoric acid substituted with an alkyl group selected from alkyl groups having 1 to 6 carbon atoms, such as a group, isopropyl group, butyl group, s-butyl group, t-butyl group, isobutyl group, pentyl group, and hexyl group Phosphoric acid monoesters such as monoesters; and dialkyl esters of phosphoric acid (eg, the two hydrogens that phosphoric acid has are methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t Two alkyl groups selected from alkyl groups having 1 to 6 carbon atoms such as butyl, isobutyl, pentyl, and hexyl groups; Phosphodiester dialkyl esters) and the like of phosphoric acid are conversion and the like. In the phosphoric acid dialkyl ester, the two alkyl groups may be the same or different from each other.

The salt of ascorbic acid phosphate is not particularly limited. For example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium, calcium and barium, and polyvalent metals such as aluminum Various metal salts such as metal salts; ammonium salts such as ammonium and tricyclohexylammonium; various alkanolamine salts such as monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, and triisopropanolamine It is done.

As the ascorbic acid phosphate and its salt used in the present invention, for example, L-ascorbic acid phosphate and its sodium salt, L-ascorbic acid phosphate and its magnesium salt are preferable, and L-ascorbic acid phosphate Magnesium salts are more preferred.

As the ascorbic acid phosphate ester and its salt, those artificially synthesized by chemical synthesis or the like may be used, or commercially available products may be used. Ascorbic acid phosphate and its salt are available from, for example, Showa Denko K.K.

As the ascorbic acid phosphate ester and salt thereof in the present invention, only one type may be used, or two or more types may be used in combination.

The compounding amount of ascorbic acid phosphate and its salt is 0.01 to 3% by mass with respect to the total mass of the agent from the viewpoint of expressing desired effects of the present invention such as an effect of enhancing the epithelial barrier function. Preferably, 0.1 to 1% by mass is more preferable.

<Vitamin E and its derivatives>
Vitamin E is a compound also called tocopherol. Vitamin E and its derivatives are not particularly limited, and examples thereof include dl-α-tocopherol, dl-tocopherol acetate, dl-α-tocopherol nicotinate, and dl-α-tocopherol succinate. Of these, dl-α-tocopherol acetate is preferred from the viewpoint of expressing the desired effect of the present invention. The dl-α-tocopherol acetate can be obtained from, for example, DSM Nutrition Japan Co., Ltd.

The blending amount of vitamin E and its derivative is preferably 0.005 to 1% by mass and more preferably 0.01 to 1% by mass with respect to the total mass of the agent from the viewpoint of expressing the desired effect of the present invention.

<Copper chlorophyll and its salt>
Copper chlorophyll is copper chlorophyllin, and can be obtained, for example, by replacing magnesium in a plant chlorophyll molecule with copper for stabilization. Examples of the salt include alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt and calcium salt. Among these, copper chlorophyllin sodium is preferable from the viewpoint of expressing the desired effect of the present invention. Copper chlorophyllin sodium is available from, for example, Wako Pure Chemical Industries, Ltd. or Kanto Chemical Co., Inc.

The blending amount of copper chlorophyll and its salt is preferably 0.00005 to 0.1% by mass, and 0.0001 to 0.01% by mass with respect to the total mass of the agent from the viewpoint of expressing the desired effect of the present invention. Is more preferable.

<Lysozyme chloride>
As lysozyme chloride, lysozyme chloride described in Japanese Pharmacopoeia (Japanese Pharmacopoeia) or makeup base (cosmetic raw material standard) obtained from chicken eggs by a known method can be used. Lysozyme chloride is available from Kewpie Corporation.

The blending amount of lysozyme chloride is preferably 0.0001 to 1% by mass and more preferably 0.001 to 0.1% by mass with respect to the total mass of the agent from the viewpoint of expressing the desired effect of the present invention.

In addition to the above component (A), the agent of the present invention further comprises (B) component: one or more selected from menthone, carvone, cineol, limonene, anethole, eugenol, menthol, and cinnamic aldehyde, May be included. As the component (B), those isolated or synthesized from essential oils may be used, or essential oils containing these may be used.

The blending amount of the component (B) is not particularly limited, but is preferably 0.00001 to 5% by mass with respect to the total mass of the agent from the viewpoint of further improving the expression of the desired effect of the present invention. More preferred is ˜2% by mass.

In the present invention, the component (B) is preferably included together with the component (A). The combined use of the component (A) and the component (B) improves the expression of the desired effect of the present invention. When the component (A) and the component (B) are used in combination, the ratio (A / B) of the mass of the component (A) to the mass of the component (B) is preferably in the following range. The ratio (A / B) of the mass of (A) ascorbic acid phosphate and its salt to the mass of component (B) is preferably 0.002 to 300,000, more preferably 0.01 to 300000, 0.05 to 300,000 is more preferable. The ratio (A / B) of the mass of (A) vitamin E and its derivative to the mass of component (B) is preferably 0.001 to 100,000, more preferably 0.01 to 100,000, and further 0.05 to 100,000. preferable. The ratio (A / B) of the mass of (A) copper chlorophyll and its salt to the mass of component (B) is preferably 0.00001 to 10000, more preferably 0.00002 to 10000, and even more preferably 0.00005 to 10000. preferable. The ratio (A / B) of the mass of (A) lysozyme chloride to the mass of component (B) is preferably 0.00002 to 100,000, more preferably 0.001 to 100,000, and even more preferably 0.005 to 100,000. When the ratio (A / B) of the mass of the component (A) to the mass of the component (B) is in the above range, the desired effect of the present invention is further improved.

In the agent of the present invention, in addition to the above components, various medicinal components and additive components known in the field of the present invention can be appropriately blended within a range not impairing the effects of the present invention.

The shape and dosage form of the agent of the present invention are not particularly limited, and for example, it can be prepared in various shapes such as liquid (liquid, liquid, paste), solid (solid, solid) and the like. Especially, it is preferable to make the agent of this invention into the composition applied to an oral cavity, and it is more preferable to set it as the composition applied to gingiva.

The agent of the present invention may be administered as it is. Moreover, you may add in order to provide the desired effect of this invention to food-drinks (especially functional food), the composition for oral cavity, and a pharmaceutical composition.

There is no restriction | limiting in particular in the food / beverage products or composition which can add the agent of this invention, For example, a drink (a soft drink, a carbonated drink, a nutrient drink, a powdered drink, a fruit drink, a milk drink, a jelly drink etc.), food (Gum, candy, tablet, gummi, film, troche, cookie, jelly, etc.).

The agent of the present invention has an effect of enhancing the epithelial barrier function. The epithelial barrier function can be rephrased as epithelial resistance. It is known that the epithelial barrier function is formed by the connection between physical epithelial cells. This intercellular connection is mainly formed by a cell junction device called tight junction and AJ. Among the epithelium, it has been reported that the mucosal epithelium has a large contribution to AJ in maintaining the barrier function, and the gingival mucosal epithelium has a greater contribution. Since E-cadherin is a major protein that constitutes AJ, the agent of the present invention is preferably in the mucosal epithelium, more preferably in the oral mucosal epithelium, still more preferably in the gingival mucosal epithelium, along with the epithelial barrier function. Resistance, intercellular binding, AJ function, and E-cadherin can be significantly enhanced.

The action of the agent of the present invention will be described.
<Enhancement of epithelial barrier function>
Strengthening the epithelial barrier function means strengthening the barrier function against the adhesion and / or invasion of pathogenic microorganisms and harmful substances against the transpiration of water and volatile components of the epithelium, and pathogenesis against the transpiration of moisture and volatile components of the epithelium. It means to strengthen the resistance against adhesion and / or invasion of sex microorganisms and harmful substances. The enhancement of the barrier function refers to an effect of improving the barrier function, an effect of suppressing a decrease in the barrier function, and an effect of improving and / or recovering the lowered barrier function. That is, the enhancement of epithelial barrier function is paraphrased as barrier function deterioration suppression, barrier function improvement and / or recovery, and the barrier function can be replaced with resistance. The application of the epithelial barrier function-enhancing agent of the present invention is preferably for mucosal epithelium, more preferably for oral mucosal epithelium, and still more preferably for gingival mucosal epithelium.

<Strengthening intercellular binding force>
The cell-to-cell binding force means the binding force that connects two cells together, and the barrier function and resistance of the epithelium are formed by the physical connection between the cells. The enhancement of intercellular binding force refers to an effect of improving the intercellular binding force, an effect of suppressing a decrease in intercellular binding force, and an effect of improving and / or recovering the intercellular binding force. That is, the enhancement of intercellular binding force can also be referred to as suppression of decrease in intercellular binding force, improvement of intercellular binding force, and / or recovery. The application of the intercellular binding strength enhancer of the present invention is preferably for mucosal epithelium, more preferably for oral mucosal epithelium, and still more preferably for gingival mucosal epithelium.

<Adhesion junction enhancement>
Adherence junction (AJ) is a cell adhesion device for the epithelium to exert intercellular binding force. The AJ function enhancement refers to an effect of improving the AJ function, an effect of suppressing a decrease in the AJ function, and an effect of improving and / or recovering the lowered AJ function. That is, AJ function enhancement is also paraphrased as AJ function deterioration suppression, AJ function improvement, and / or recovery. The application of the AJ function-enhancing agent of the present invention is preferably for mucosal epithelium, more preferably for oral mucosal epithelium, and still more preferably for gingival mucosal epithelium.

<Strengthened E-cadherin>
E-cadherin is an epithelial cadherin as described above. Enhancement of E-cadherin refers to an effect of increasing the expression of E-cadherin, an effect of suppressing a decrease in the expression of E-cadherin, and an effect of improving and / or recovering the decreased expression of E-cadherin. That is, E-cadherin enhancement is also referred to as suppression of E-cadherin lowering, improvement of E-cadherin expression, and / or recovery. The application of the E-cadherin enhancer of the present invention is preferably for mucosal epithelium, more preferably for oral mucosal epithelium, and still more preferably for gingival mucosal epithelium.

The epithelial barrier function-enhancing agent, resistance-enhancing agent, intercellular binding-enhancing agent, adherence-junction function-enhancing agent, and E-cadherin-enhancing agent of the present invention are used to prevent a normal state from becoming an abnormal state. It may be used, or may be used to restore an abnormal state to a normal state.

In addition, since the agent of the present invention has an epithelial barrier function-enhancing action, a resistance-enhancing action, an intercellular binding-force-enhancing action, an adherence-junction function-enhancing action, and an E-cadherin-enhancing action, It is useful for maintaining or restoring the mucosa, gastrointestinal mucosa and oral mucosa in a healthy state, and particularly useful for maintaining the healthy state of the mucosal epithelium. The agent of the present invention is more preferably used in the oral mucosal epithelium, more preferably in the gingival mucosal epithelium.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the embodiments.

[Evaluation Test Example 1] Evaluation of E-cadherin reinforcing effect Human gingival epithelial cells were seeded in a 96-well plate and cultured to confluence in the medium Humedia-KG2 (Kurabo Co., Ltd.) to express the epithelial barrier function. A cell membrane was prepared. Thereafter, 0.01 mass% of lipopolysaccharide (Pg-LPS) derived from Porphyromonas gingivalis (Pg bacteria) or 0.01 mass% of LPS (E. coli-LPS) derived from Escherichia coli (E. coli bacteria), Component (A) (one or more selected from tocopherol acetate, copper chlorophyllin sodium, lysozyme chloride and magnesium ascorbate phosphate), component (B) (menton, carvone, cineol, limonene, anethole, eugenol, menthol and cinnamic) One or more selected from aldehydes) and a comparative compound shown in Table 5 (sodium selected from sodium ascorbate, sodium hyaluronate, sodium azulene sulfonate and menthol) One or more selected from, the amounts listed in Table, in Humedia-KG2 was added simultaneously to prepare a cultured evaluation sample 3 days. Here, Pg-LPS is an LPS derived from Pg bacteria that has been reported to have an effect on the gingival epithelium and systemic epithelium. E. coli-LPS has also been reported to affect the intestinal mucosal epithelium. These LPS are known as pathogenic substances derived from bacteria, and have an action of promoting E-cadherin destruction.

For each of the obtained evaluation samples, E-cadherin expressed in human gingival epithelial cells is immunofluorescent-stained, and the fluorescence intensity in each evaluation sample is defined as E-cadherin with the fluorescence intensity of the healthy barrier model (untreated) as 100%. The expression rate was calculated. In addition, the healthy barrier model includes Humedia-KG2, 0.01% by mass of Pg-LPS or 0.01% by mass of E. coli. Coli-LPS was added and cultured for 3 days. The cells with reduced E-cadherin expression were used as controls (at the time of LPS alone treatment), and the inhibition rate of E-cadherin expression decrease was determined by the following formula (1). To Table 5.

When calculating the inhibition rate of E-cadherin expression decrease for an evaluation sample using Pg-LPS as LPS, the control E-cadherin expression rate when Pg-LPS was added alone was used. When calculating the inhibition rate of E-cadherin expression reduction for an evaluation sample using E. coli-LPS, The E-cadherin expression rate of the control to which E. coli-LPS was added alone was used.

In the columns of additive components in Tables 1 to 4, the additive components and amounts used in each treatment example are described. Specifically, in the column of additive component, the type and amount of LPS, the compound used as component (A) and its concentration in sample (mass%), and the compound used as component (B) and concentration in sample (mass) In addition, the column of additive components in Table 5 shows the types and amounts of LPS, and comparative compounds used in place of the components (A) and (B) (sodium ascorbate, sodium hyaluronate, azulene). Sodium sulfonate and menthol) and their concentration (mass%) in the sample.

[Evaluation Test Example 2] Barrier Function Evaluation Test After seeding a human gingival epithelial cell line on the upper layer of the culture insert (Millipore) and culturing it to confluence in the basic medium Humedia-KG2 to produce an epithelial cell membrane expressing the epithelial barrier function In addition to the single medium supplemented with 0.01% by mass of Pg-LPS and 0.01% by mass of Pg-LPS, the component (A) (tocopherol acetate, copper chlorophyllin sodium, lysozyme chloride and 1 or more types selected from magnesium salts of ascorbic acid phosphate ester), (B) component (one or more types selected from menthone, carvone, cineol, limonene, anethole, eugenol, menthol and cinnamic aldehyde), and Table 5 Compound of (sodium ascorbate, hyal One or more kinds selected from sodium ronate, sodium azulene sulfonate and menthol were cultured for 3 days in the amount of the medium listed and added medium. After culturing, the upper and lower media were removed and washed, and the barrier function of the epithelial cell membrane was evaluated. For barrier function evaluation, permeation experiment of LPS (P.g-LPS) which is a bacterium-derived toxin, permeation experiment of bacteria (Streptococcus mitis (S. m)), and electrical resistance value (TER) measurement assay of epithelial cell membrane went.
Here, LPS is a pathogenic substance derived from bacteria, and is known to exist as a macromolecule by forming a colloid in an aqueous solution. S. m bacteria are known to be resident in the oral mucosa, and are generally known to cause purulent inflammation when the pathogenicity is low but the epithelial barrier function is reduced. TER is known to have a strong correlation with the barrier function of the cell layer, and is mainly related to the permeability of moisture and ions, and it is reported that the higher the TER value in the cosmetics field, the better the moist feeling of the skin. Has been.

(Pg-LPS permeation experiment)
For the epithelial cell membrane after 3 days of culture, 0.2 mL of Humedia-KG2 adjusted to 0.01% by adding Pg-LPS was added to the upper layer, and 0.9 mL of Humedia-KG2 was added to the lower layer. After 4 hours, P. The g-LPS concentration was quantified with Pyrochrome (Seikagaku Corporation), the barrier function was calculated from the following formula (2) using the quantified value, and the results are shown in Tables 1 to 5 (LPS concentration in the lower layer, relative to LPS) Barrier function).

(Permeation experiment of S.m bacteria)
The epithelial cell membrane after 3 days of culture was transformed into S. cerevisiae in a medium in which antibiotics were removed from the Humeria-KG2 medium. A medium prepared by suspending m. m. bacterium and adjusting to 10 ⁷ cells / mL is 0.2 mL in the upper layer. 0.9 mL of m-free medium was added to the lower layer, and 20 μL was collected from the lower layer after 4 hours, appropriately diluted, and seeded on a tryptic soy agar medium. The seeded medium was cultured for 48 hours under an aerobic condition at 37 ° C., and the concentration of lower layer bacteria (CFU / mL) was calculated from the number of colonies and the dilution rate of the medium, and are shown in Tables 1 to 5. Furthermore, the barrier function against the bacteria was calculated from the following formula (2) using the bacteria concentration in the lower layer, and are shown in Tables 1 to 5.

(TER measurement)
The TER (Ω · cm ² ) was calculated by multiplying the value (Ω) measured using Millicell-ERS Volto-Om Meter by the cell layer area (cm ² ). Furthermore, using this TER value, the barrier function against ions and moisture was calculated from the following formula (2), and the results are shown in Tables 1 to 5.

In this evaluation test example, although the preparation method of the evaluation sample is different from evaluation test example 1, the additive component added to the culture medium and the amount thereof correspond to the additive component of evaluation test example 1, and thus the evaluation test. About the thing with the same addition component as Example 1, the result of this evaluation test example was written in the place of the corresponding treatment example.

[Results and discussion]
(About cadherin expression rate)
As shown in the table, Treatment Example 1 containing (A) component (at least one selected from the group consisting of ascorbic acid phosphate and its salt, tocopherol acetate, copper chlorophyll and its salt, and lysozyme chloride) as an additional component In -76, the E-cadherin expression rate was higher than that of the sample to which only LPS was added, and the E-cadherin expression decrease suppression rate was 9.1% or more. Particularly, in the treatment examples 6 to 17, 19, 25 to 36, 38, 44 to 55, 57, 63 to 74, and 76 that further include the component (B) in addition to the component (A), the E-cadherin expression rate is 90%. As described above, the inhibition rate of E-cadherin expression decrease was 69.7% or more.
On the other hand, in the treatment examples 77 to 80 where the treatment was performed with the additive component not containing the component (A), the E-cadherin expression rate was lower than that of the sample to which only LPS was added, and the E-cadherin expression decrease suppression rate was negative. The decrease in expression could not be suppressed.
From this, it was found that according to the present invention, the E-cadherin expression rate was increased, so that the E-cadherin strengthening effect was exhibited. Further, it was found that the component containing the component (B) together with the component (A) is preferable in expressing the E-cadherin enhancing effect because the expression rate of E-cadherin is increased.

(About barrier function)
As shown in the table,
In the treatment examples 1 to 76 containing the component (A) (at least one selected from the group consisting of ascorbic acid phosphate and its salt, tocopherol acetate, copper chlorophyll and its salt, and lysozyme chloride) as an additional component, no treatment The barrier function against LPS, bacteria, and ionic moisture was higher than that of the sample. Particularly, in the treatment examples 6 to 17, 19, 25 to 36, 38, 44 to 55, 57, 63 to 74, and 76 that further contain the component (B) in addition to the component (A), the barrier against LPS, bacteria, and ionic moisture The function was high.
On the other hand, in the treatment examples 77 to 80 where the treatment was performed with the additive component not containing the component (A), the barrier functions against LPS, bacteria, and ionic water were all lower than those without treatment.
From this, it was found that according to the present invention, the barrier function against LPS, bacteria, ions and moisture is high. Moreover, it turned out that what contains (B) component with (A) component has a high barrier function especially with respect to LPS, bacteria, ions, and moisture.

[Prescription example]
Also in the prescription shown below, the enhancement effect of the barrier function is confirmed as in the examples.

Formulation Example 1
(1) For skin (mass%)
a) Tocopherol acetate 0.5
b) Decaglyceryl monolauroylate 0.2
c) Diglyceryl monoisostearate 0.1
d) Polyoxyethylene hydrogenated castor oil (60 EO) 1.0
e) Concentrated glycerin 8.0
f) Methylparaben 0.3
g) Propylparaben 0.1
h) Hydroxyethylcellulose 0.1
i) Ethanol 12.0
j) Purified water balance
Total 100.0

Formulation Example 2
(2) For skin (mass%)
a) Magnesium phosphate ascorbate 0.1
b) Decaglyceryl monolauroylate 0.2
c) Diglyceryl monoisostearate 0.1
d) Polyoxyethylene hydrogenated castor oil (60 EO) 1.0
e) Concentrated glycerin 8.0
f) Methylparaben 0.3
g) Propylparaben 0.1
h) Hydroxyethylcellulose 0.1
i) Ethanol 12.0
j) Purified water balance
Total 100.0

Formulation Example 3
(3) For mucosal epithelium (mass%)
a) Tocopherol acetate 0.1
b) Squalane 10.0
c) cetostearyl alcohol 4.0
d) Methylpolysiloxane 3.0
e) Cetyl palmitate 2.0
f) Glycerol monostearate 1.5
g) Concentrated glycerin 12.0
h) 1,3-butylene glycol 2.0
i) Carboxyvinyl polymer 0.15
j) Methylparaben 0.3
k) Sodium hydroxide appropriate amount
l) Purified water balance
Total 100.0

Formulation Example 4
(4) For mucosal epithelium (mass%)
a) Magnesium phosphate ascorbate 0.3
b) Squalane 10.0
c) cetostearyl alcohol 4.0
d) Methylpolysiloxane 3.0
e) Cetyl palmitate 2.0
f) Glycerol monostearate 1.5
g) Concentrated glycerin 12.0
h) 1,3-butylene glycol 2.0
i) Carboxyvinyl polymer 0.15
j) Methylparaben 0.3
k) Sodium hydroxide appropriate amount
l) Purified water balance
Total 100.0

Formulation Example 5
(5) For oral epithelium (mass%)
a) Tocopherol acetate 0.5
b) Ethanol 20.0
c) Polyvinylpyrrolidone 10.0
d) Hydroxypropyl methylcellulose 0.3
e) Sodium carboxymethylcellulose 0.5
f) Glycerin 25.0
g) Polyoxyethylene sorbitan stearate 0.2
h) Sodium hydroxide appropriate amount i) Perfume appropriate amount
j) Purified water balance
Total 100.0

Formulation Example 6
(6) For oral epithelium (mass%)
a) Ascorbic acid phosphate magnesium 1.0
b) Ethanol 20.0
c) Polyvinylpyrrolidone 10.0
d) Hydroxypropyl methylcellulose 0.3
e) Sodium carboxymethylcellulose 0.5
f) Glycerin 25.0
g) Polyoxyethylene sorbitan stearate 0.2
h) Sodium hydroxide appropriate amount i) Perfume appropriate amount
j) Purified water balance
Total 100.0

Formulation Example 7
(7) For gingival epithelium (mass%)
a) Tocopherol acetate 0.1
b) Carboxyvinyl polymer 2.2
c) Hydroxypropyl methylcellulose 0.3
d) Glycerin 23.0
e) Ethanol 12.0
f) Methylparaben 3.0
g) Polysorbate 60 0.15
h) Sorbitan monostearate 0.1
i) Sucrose fatty acid ester 0.5
j) Light liquid paraffin 0.5
k) perfume appropriate amount l) sodium hydroxide appropriate amount m) potassium hydroxide appropriate amount n) citric acid appropriate amount
o) Purified water balance
Total 100.0

Formulation Example 8
(8) For gingival epithelium (mass%)
a) Magnesium phosphate ascorbate 0.3
b) Carboxyvinyl polymer 2.2
c) Hydroxypropyl methylcellulose 0.3
d) Glycerin 23.0
e) Ethanol 12.0
f) Methylparaben 3.0
g) Polysorbate 60 0.15
h) Sorbitan monostearate 0.1
i) Sucrose fatty acid ester 0.5
j) Light liquid paraffin 0.5
k) perfume appropriate amount l) sodium hydroxide appropriate amount m) potassium hydroxide appropriate amount n) citric acid appropriate amount
o) Purified water balance
Total 100.0

Formulation Example 9
(9) For gingival epithelium (mass%)
a) Tocopherol acetate 0.6
b) Carboxyvinyl polymer 2.2
c) Hydroxypropyl methylcellulose 0.3
d) Glycerin 23.0
e) Ethanol 12.0
f) Methylparaben 3.0
g) Polysorbate 60 0.15
h) Sorbitan monostearate 0.1
i) Sucrose fatty acid ester 0.5
j) Light liquid paraffin 0.5
k) perfume appropriate amount l) sodium hydroxide appropriate amount m) potassium hydroxide appropriate amount n) citric acid appropriate amount
o) Purified water balance
Total 100.0

Claims

An adherence junction function-enhancing agent containing at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
The reinforcing agent according to claim 1, which is for mucosal epithelium.
The reinforcing agent according to claim 1, which is for oral epithelium.
The reinforcing agent according to claim 1, which is for gingival epithelium.
An E-cadherin fortifier containing at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
The reinforcing agent according to claim 5, which is for mucosal epithelium.
The reinforcing agent according to claim 5, which is for oral epithelium.
The reinforcing agent according to claim 5, which is for gingival epithelium.
An intercellular binding enhancer containing at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
The reinforcing agent according to claim 9, which is for mucosal epithelium.
The reinforcing agent according to claim 9, which is for oral epithelium.
The reinforcing agent according to claim 9, which is for gingival epithelium.
An ascorbic acid phosphate ester and salt thereof, vitamin E and derivatives thereof, copper chlorophyll and salt thereof, and at least one selected from the group consisting of lysozyme chloride, an epithelial barrier function enhancer.
The reinforcing agent according to claim 13, which is for mucosal epithelium.
The reinforcing agent according to claim 13, which is for oral epithelium.
The reinforcing agent according to claim 13, which is for gingival epithelium.
A resistance enhancer containing at least one selected from the group consisting of ascorbic acid phosphate and salts thereof, vitamin E and derivatives thereof, copper chlorophyll and salts thereof, and lysozyme chloride.
The reinforcing agent according to claim 17, which is for mucosal epithelium.
The reinforcing agent according to claim 17, which is for oral epithelium.
The reinforcing agent according to claim 17, which is for gingival epithelium.
Further, one or more selected from menthone, carvone, cineol, limonene, anethole, eugenol, menthol and cinnamic aldehyde,
The toughening agent according to any one of claims 1 to 20, comprising