CN107106539A - It is adhesively joined function intensified dose - Google Patents
It is adhesively joined function intensified dose Download PDFInfo
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- CN107106539A CN107106539A CN201580071316.2A CN201580071316A CN107106539A CN 107106539 A CN107106539 A CN 107106539A CN 201580071316 A CN201580071316 A CN 201580071316A CN 107106539 A CN107106539 A CN 107106539A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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Abstract
The present invention provide be adhesively joined function intensified dose, E cadherins hardening agent, iuntercellular adhesion hardening agent, function intensified dose of epithelial barrier and resistance hardening agent, above-mentioned preparation contains selected from ascorbic acid phosphoric acid esters and its salt, vitamin E and its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
Description
Technical field
The present invention relates to be adhesively joined function intensified dose, CAM 120/80 hardening agent, iuntercellular adhesion hardening agent, epithelium
Barrier function hardening agent, resistance hardening agent.
Background technology
Epithelium refers to that epiderm skin, nasal cavity, respiratory tract, oral cavity, alimentary canal, genitourinary/urogenital mucous membrane etc. cover body
Surfaces externally and internally cellular layer.Epithelium, which possesses to have, to be prevented moisture evaporation, prevents by from outside chemical irritation or physical
Barrier function in the caused damage of stimulation, pathogenic microbes intrusive body, to sustaining life, body plays an important role.On known
The barrier function of skin can be reduced due to pressure, ultraviolet, temperature, humidity, infectious microorganism etc., and the barrier function of epithelium
Decline it is relevant with the morbidity of a variety of illness.Therefore, for the healthy purpose for keeping skin condition, people are in skin table
Preparation for external application to skin containing skin barrier function improver etc. (referenced patent document 1) has been attempted on skin.Similarly, it is known that dimension
Gut barrier function is held, prevention and/or improvement that the morbidity or enteritis for insulin resistance caused by obesity are aggravated
Critically important, people have also attempted the research and development (referenced patent document 2) of epidermis, epithelial barrier function-improving agent on mucous membrane.
It is known that epithelial barrier function is by formed by the physical connection between epithelial cell.This iuntercellular
Connection is by being referred to as closely connecting, being adhesively joined (Adherence junction；Hereinafter also referred to as " AJ ") or gap
Formed by the cell adherence structure of connection.It is known that, AJ plays a crucial role in cell adherence structure, AJ shape
Into being that to form other cell adherence structures institute indispensable (referring to non-patent literature 1,2,3).
It is currently known in its family to have about 20 kinds of cadherins, it is known that to be present in skin on cadherin (cadherin)
The species of the cadherin of skin epidermis is E (epitheliated type)-cadherin, it was reported that similarly expression has E- calcium in people's epithelial tissue
Mucoprotein (refers to non-patent literature 4).
On CAM 120/80, it is the main composition for the AJ for playing the important function for maintaining epithelial barrier function,
According to report and suggestion, in disease (reflux esophagitis, IBD, the anaphylaxis lost with epithelial barrier function
Rhinitis, stomatitis, periodontosis, dry, halitosis etc.) in, the expression reduction of CAM 120/80 controls the CAM 120/80 in epithelium
Expression for disease prevention and/or treat it is critically important.For example, a kind of preparation for external application to skin has been recorded in patent document 1, its
It is absorbed in the CAM 120/80 as E cadherin, by promoting the expression of the CAM 120/80 in application on human skin, is used to
The wrinkle of improvement skin, relaxation, skin pattern structure.
[prior art literature]
[patent document]
[patent document 1] Japanese Patent Laid-Open 2007-001914 publications
[patent document 2] Japanese Patent Laid-Open 2011-178764 publications
[non-patent literature 1] Barry Gumbiner etc., The Journal of Cell Biology, in 1988
Volume 107, the 1575-1587 pages
[non-patent literature 2] Barry M.Gumbiner.Nature Reviews, volume 6, the 622-634 pages in 2005
[non-patent literature 3] Wim.F.Jongen etc., The Journal of Cell Biology, volume 114, in 1991
3 phases, the 545-555 pages
[non-patent literature 4] Anne B.Katz etc., Journal of Investigative Dermatology, in 1999
Volume 112, the 5th phase, the 818-821 pages
The content of the invention
The solved problem of invention
It is known that epithelium is separates the tissue of the inner side and outer side of life entity, for the weight in terms of the body that sustains life
The evaporation or the invasion of pathogenic microbes of moisture or ion are wanted, epithelium has physical barrier function.It is believed that this
The reason for reduction of kind barrier function can turn into a variety of disease incidences.Accordingly, there exist the new of the barrier function for providing reinforcing epithelium
The potential demand of type preparation.
The purpose of the problem of the present invention is to provide a kind of preparation for strengthening epithelial barrier function.
The means to solve the problem
The present invention is in view of the invention that the above is completed, it is found that ascorbic acid phosphoric acid esters and its salt, vitamin E
And its derivative, copper chlorophyll and its salt and lysozyme chloride have reinforcing epithelium by strengthening the expression of CAM 120/80
The effect of barrier function, so as to complete the present invention.
The present invention provides following [1]~[21].
[1] one kind is adhesively joined function intensified dose, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E
And its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
[2] hardening agent according to [1], it is the hardening agent of mucous epithelium.
[3] hardening agent according to [1], it is the hardening agent of oral mucous epithelia.
[4] hardening agent according to [1], it is the hardening agent of gingival mucosa epithelium.
[5] a kind of CAM 120/80 hardening agent, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E and
Its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
[6] hardening agent according to [5], it is the hardening agent of mucous epithelium.
[7] hardening agent according to [5], it is the hardening agent of oral mucous epithelia.
[8] hardening agent according to [5], it is the hardening agent of gingival mucosa epithelium.
[9] a kind of iuntercellular adhesion hardening agent, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E
And its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
[10] hardening agent according to [9], it is the hardening agent of mucous epithelium.
[11] hardening agent according to [9], it is the hardening agent of oral mucous epithelia.
[12] hardening agent according to [9], it is the hardening agent of gingival mucosa epithelium.
[13] function intensified dose of a kind of epithelial barrier, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin
E and its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
[14] hardening agent according to [13], it is the hardening agent of mucous epithelium.
[15] hardening agent according to [13], it is the hardening agent of oral mucous epithelia.
[16] hardening agent according to [13], it is the hardening agent of gingival mucosa epithelium.
[17] one species resistance hardening agents, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E and its
Derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
[18] hardening agent according to [17], it is the hardening agent of mucous epithelium.
[19] hardening agent according to [17], it is the hardening agent of oral mucous epithelia.
[20] hardening agent according to [17], it is the hardening agent of gingival mucosa epithelium.
[21] hardening agent according to any one of [1]~[20], it, which also contains, is selected from menthones, carvol, cineole, lemon
It is more than one or both of lemon alkene, anethole, eugenol, menthol and cinnamic acid.
Invention effect
According to the present invention, it can effectively strengthen epithelial barrier function.
Embodiment
The preparation of the present invention contain selected from ascorbic acid phosphoric acid esters and its salt, vitamin E and its derivative, copper chlorophyll and
At least one of its salt and lysozyme chloride (hereinafter referred to as " (A) composition ").
<Ascorbic acid phosphoric acid esters and its salt>
As ascorbic acid phosphoric acid esters and its salt, for example, it can enumerate each by 2 of ascorbic acid, 3,5 and 6 with phosphoric acid
Individual hydroxyl carries out the material of esterification.As long as more than one of the esterification position of ascorbic acid in each above-mentioned hydroxyl is
Can.
As the phosphoric acid in ascorbic acid phosphoric acid esters, it is not particularly limited, for example, can enumerates phosphoric acid；The monoalkyl ester of phosphoric acid
(for example, the hydrogen that phosphoric acid has is selected from methyl, ethyl, propyl group, isopropyl, butyl, sec-butyl, the tert-butyl group, isobutyl
The phosphate monoester that the carbon numbers such as base, amyl group and hexyl are replaced by the alkyl in the alkyl of 1~6) etc. phosphate monoester；With
And, the dialkyl ester of phosphoric acid (for example, two hydrogen that phosphoric acid has be selected from methyl, it is ethyl, propyl group, isopropyl, butyl, secondary
The phosphoric acid that the carbon numbers such as butyl, the tert-butyl group, isobutyl group, amyl group and hexyl are replaced by two alkyl in the alkyl of 1~6
Dialkyl ester) etc. di-phosphate ester.In the dialkyl ester of the phosphoric acid, two alkyl can be same to each other or different to each other.
As the salt of ascorbic acid phosphoric acid esters, be not particularly limited, the alkali metal salt such as can enumerate sodium, potassium, magnesium, calcium and
The alkali salts such as barium, and, the various metal salts such as multivalent metal salt such as aluminium；The ammonium salts such as ammonium, thricyclohexyl ammonium；MEA,
Various alkanol amine salts such as diethanol amine, triethanolamine, monoisopropanolamine, diisopropanolamine (DIPA), triisopropanolamine etc..
As the ascorbic acid phosphoric acid esters and its salt for the present invention, for example, it is preferable to L-AA phosphate and its sodium
Salt, L-AA phosphate and its magnesium salts, more preferably APM salt.
Ascorbic acid phosphoric acid esters and its salt can be used via the artificial synthesized material such as chemical synthesis, it would however also be possible to employ commercially available
Product.Ascorbic acid phosphoric acid esters and its salt from Showa electrician (strain) such as can buy.
Ascorbic acid phosphoric acid esters and its salt in the present invention, can be used only one kind, also can be combined using two or more.
From desired effect of the invention is shown such as the angle the effect for strengthening epithelial barrier function, to make
The combined amount of the gross mass meter of agent, ascorbic acid phosphoric acid esters and its salt is preferably 0.01~3 mass %, more preferably 0.1~1 matter
Measure %.
<Vitamin E and its derivative>
Vitamin E is a kind of compound for being also referred to as tocopherol (tocopherol).As vitamin E and its derivative,
It is not particularly limited, for example, can enumerates dl- alpha-tocopherols, dl- tocopherol acetates, dl- Tocopheryl Nicotinates, dl- α-life
Educate phenol succinate etc..Wherein, from the angle for showing desired effect of the invention, preferably dl- alpha-tocopherols acetic acid
Ester.Dl- alpha-tocopherol acetates from DSM Nutrition Japan (strain) such as can buy.
From the angle for showing desired effect of the invention, in terms of the gross mass of preparation, vitamin E and its derivative
The combined amount of thing is preferably 0.005~1 mass %, more preferably 0.01~1 mass %.
<Copper chlorophyll and its salt>
Copper chlorophyll refers to copper pheophytin (copper chlorophyllin), for example, by using copper the leaf in plant can be replaced green
Magnesium in plain molecule, stabilizing it and obtain.As its salt, the alkali metal salts such as sodium salt, sylvite, calcium salt or alkaline earth gold can be enumerated
Belong to salt.Wherein, from the angle for showing desired effect of the invention, preferably chlorophyll copper sodium.Chlorophyll copper sodium is for example
It can be bought from Wako Pure Chemical Industries (strain) or the Northeast chemical (strain) etc..
From the angle for showing desired effect of the invention, in terms of the gross mass of preparation, copper chlorophyll and its salt
Combined amount be preferably 0.00005~0.1 mass %, more preferably 0.0001~0.01 mass %.
＜ lysozyme chlorides ＞
As lysozyme chloride, the Japanese Pharmacopoeia (Pharmacopeia of Japan) or adornment obtained by known method from egg can be used
The lysozyme chloride that former base (cosmetic material benchmark) is recorded.Lysozyme chloride can be from mound ratio (strain) (kewpie
) etc. corporation buy.
From the angle for showing desired effect of the invention, in terms of the gross mass of preparation, lysozyme chloride it is mixed
Resultant is preferably 0.0001~1 mass %, more preferably 0.001~0.1 mass %.
The preparation of the present invention, beyond (A) composition, can also contain (B) composition：Selected from menthones, carvol, eucalyptus
It is more than one or both of brain, limonene, anethole, eugenol, menthol and cinnamic acid.As (B) composition, it can be used
The material or the material of synthesis isolated from essential oil, it is possible to use the essential oil containing these materials.
(B) combined amount of composition is not particularly limited, from the angle for the performance for further improving desired effect of the invention
Degree sets out, in terms of the gross mass of preparation, preferably 0.00001~5 mass %, more preferably 0.00001~2 mass %.
In the present invention, preferably contain (B) composition while containing (A) composition.By by (A) composition and (B) composition one
Rise and use, further improve the performance of desired effect of the invention.By (A) composition when (B) composition is used together, (A) into
The quality divided is preferably following scope with respect to the ratio (A/B) of the quality of (B) composition.(A) ascorbic acid phosphoric acid esters and its salt
Quality is preferably 0.002~300000 with respect to the ratio (A/B) of the quality of (B) composition, and more preferably 0.01~300000, further
Preferably 0.05~300000.(A) quality of vitamin E and its derivative is preferably with respect to the ratio (A/B) of the quality of (B) composition
0.001~100000, more preferably 0.01~100000, more preferably 0.05~100000.(A) copper chlorophyll and its salt
Quality with respect to the ratio (A/B) of quality of (B) composition be preferably 0.00001~10000, more preferably 0.00002~10000,
More preferably 0.00005~10000.(A) quality of lysozyme chloride is preferred with respect to the ratio (A/B) of the quality of (B) composition
For 0.00002~100000, more preferably 0.001~100000, more preferably 0.005~100000.If by (A) composition
Quality be scheduled on scope as described above with respect to the ratio (A/B) of quality of (B) composition, then will further improve desired by the present invention
Effect performance.
, can be appropriate mixed in the range of the effect of the present invention is not damaged beyond above-mentioned each composition in the preparation of the present invention
Close known various medicinal ingredients and adding ingredient in field of the present invention.
The present invention preparation form and formulation be not particularly limited, for example may be modulated as liquid-type (liquid, liquid,
Pulpous state), the various forms such as solid type (solid, solid-state).Wherein, preparation of the invention is preferably prepared as the combination suitable for oral cavity
Thing, is more preferably prepared as the composition suitable for gum.
The preparation of the present invention can also be bestowed directly.In addition, also (feature food can be particularly in beverage/food
Product), composition for oral cavity, in medical composition, be added to assign desired effect of the invention.
The beverage/food or composition that the preparation of the present invention can be added are not particularly limited, for example, can enumerate beverage (clear
Cool beverage, soda, nutritious drink, powder drink, fruit nectar, milk beverage, frozen glue beverage etc.), foodstuff (chewing gum
(gum), candy, tablet (tablet), chewing gum (gummi), film (film), lozenge (troche), biscuit, frozen glue
(jelly)) etc..
The preparation of the present invention has the effect of reinforcing epithelial barrier function.The barrier function of epithelium is also referred to as epithelium
Resistance.It is known that the barrier function of epithelium is by formed by the physical connection between epithelial cell.The iuntercellular connects
Connect mainly by closely connect and referred to as AJ cell adherence structure and formed.It is reported that on the mucous membrane among epithelium
The contribution degree of Pi Zhong, AJ in terms of barrier function maintenance is very big, and further its contribution degree is bigger in gingival mucosa epithelium.Due to
CAM 120/80 be constitute AJ main protein, therefore the present invention preparation preferably in mucous epithelium, more preferably in oral cavity
Mucous epithelium, further preferably while can significantly strengthen epithelial barrier function in gingival mucosa epithelium, can also be significantly
Strengthen epithelium resistance, iuntercellular adhesion, AJ functions and CAM 120/80.
Effect to the preparation of the present invention is illustrated.
<Epithelial barrier is function intensified>
Epithelial barrier is function intensified to be referred to, reinforcing epithelium have for moisture and volatile ingredient it is evaporation, for cause of disease
Property microorganism and harmful substance attachment and/or invasion barrier function, reinforcing epithelium have for moisture and evaporating into
The resistance of attachment and/or the invasion evaporation, for pathogenic microbes and harmful substance that divide.Barrier function reinforcing refers to
Effect, the effect for suppressing barrier function reduction, the effect for the barrier function for improving and/or recovering reduction for improving barrier function.
That is, epithelial barrier is function intensified alternatively referred to as suppresses barrier function reduction, improves and/or recovers barrier function, barrier function
It is changed to resistance.At the applicable aspect of function intensified dose of the epithelial barrier of the present invention, preferably mucous epithelium is used, more preferably
Oral mucous epithelia is used, and particularly preferably gingival mucosa epithelium is used.
<Iuntercellular adhesion is strengthened>
Iuntercellular adhesion means the adhesion between two cells of connection, and the barrier function and resistance that epithelium has are logical
Formed by the physical connection crossed between its cell.Iuntercellular adhesion reinforcing refer to improve iuntercellular adhesion effect,
Suppress the effect of iuntercellular adhesion reduction, improve and/or recover the effect of iuntercellular adhesion.That is, iuntercellular adhesion is strong
Change and alternatively referred to as suppress the reduction of iuntercellular adhesion, improve and/or recover iuntercellular adhesion.Combined in the iuntercellular of the present invention
The applicable aspect of power hardening agent, preferably mucous epithelium are used, and more preferably oral mucous epithelia is used, and more preferably gum glues
Film epithelium is used.
<It is adhesively joined function intensified>
It is adhesively joined (AJ) and refers to cell adherence structure of the epithelium to play iuntercellular adhesion.AJ is function intensified to be referred to improve
The effect of the effect of AJ functions, the effect for suppressing the reduction of AJ functions, the AJ functions of improving and/or recover reduction.That is, AJ functions are strong
Change and alternatively referred to as suppress the reduction of AJ functions, improve and/or recover AJ functions.In function intensified dose of the AJ of the present invention applicable side
Face, preferably mucous epithelium are used, and more preferably oral mucous epithelia is used, and more preferably gingival mucosa epithelium is used.
<CAM 120/80 is strengthened>
As described above, CAM 120/80 is the cadherin of epitheliated type.CAM 120/80 reinforcing refers to strengthen CAM 120/80
The effect of expression, the effect for expressing reduction for suppressing CAM 120/80, the expression for the CAM 120/80 for improving and/or recovering reduction
Effect.That is, CAM 120/80 reinforcing alternatively referred to as suppresses CAM 120/80 reduction, improves and/or recovers CAM 120/80 table
Reach.At the applicable aspect of the CAM 120/80 hardening agent of the present invention, preferably mucous epithelium is used, more preferably oral mucous epithelia
With more preferably gingival mucosa epithelium is used.
Function intensified dose of the epithelial barrier of the present invention, resistance hardening agent, iuntercellular adhesion hardening agent, it is adhesively joined work(
Energy hardening agent and CAM 120/80 hardening agent both can be used to prevent normal condition to be changed into abnormality, it is also possible to so that abnormality
Revert to normal condition.
In addition, the preparation of the present invention is due to the function intensified effect of epithelial barrier, resistance invigoration effect, iuntercellular knot
With joint efforts invigoration effect, be adhesively joined it is function intensified effect, CAM 120/80 invigoration effect, therefore keep or recover skin, eye
It is useful in terms of mucous membrane, schneiderian membrane, gastrointestinal mucosa, the health status of oral mucosa, particularly keeping the healthy shape of mucous epithelium
It is useful in terms of state.The preparation of the present invention is useful more preferably in oral mucous epithelia, further preferably in gingival mucosa epithelium
It is useful.
Embodiment
The present invention is described in more detail below in association with embodiment, but the present invention is not by the reality of these embodiments
Apply the restriction of mode.
[evaluation test example 1] CAM 120/80 strengthens the evaluation of effect
Human gingival epithelial cells are inoculated with 96 orifice plates, (Cangfu is twisted flax fibers and woven (kurabo) strain formula meeting using culture medium Humedia-KG2
Society) culture is to cell confluency, and making shows the epithelial cell membrane of epithelial barrier function.Then, it is (same using Humedia-KG2
When be added with：The 0.01 mass % fat from porphyromonas gingivalis (Porphyromonas gingivalis, Pg bacterium) is more
Sugared (Pg-LPS) or 0.01 mass the % LPS (E.coli- from Escherichia coli (Escherichia coli, E.coli bacterium)
LPS)；And, it is (molten selected from tocopherol acetate, chlorophyll copper sodium, chlorination selected from (A) composition according to amount described in table
One or more of magnesium salts of bacterium enzyme and ascorbic acid phosphoric acid esters), (B) composition (be selected from menthones, carvol, cineole, lemon
One or more of alkene, anethole, eugenol, menthol and cinnamic acid) and table 5 described in comparative compound (be selected from
One or more of sodium ascorbate, Sodium Hyaluronate, sodium azulenesulfonate and menthol) more than one), cultivate three days, make
Evaluate sample.Herein, Pg-LPS is from it is reported that the LPS, E.coli- of the Pg bacterium of gingival epithelium and whole body epithelium can be influenceed
LPS is from it is reported that the LPS of the E.coli bacterium of epithelium of intestinal mucosa can be influenceed, it is known that these LPS are the disease from bacterium
Immunogenic substance, the effect with the destruction for promoting CAM 120/80.
For each evaluation sample of gained, immunofluorescence is carried out to the CAM 120/80 expressed in Human gingival epithelial cells
Dyeing, the fluorescence intensity using healthy normal barrier sample (untreated) calculates each fluorescence evaluated in sample strong as 100%
Degree, is used as CAM 120/80 expression rate.In addition, adding Humedia-KG2,0.01 mass % in healthy normal barrier sample
Pg-LPS or 0.01 mass % E.coli-LPS, cultivate three days so that CAM 120/80 expression reduction cell conduct
Control group (when LPS is individually handled), the inhibiting rate of CAM 120/80 expression reduction is obtained by following formula (1), is represented in 1~table of table
In 5.
[number 1]
The inhibiting rate of CAM 120/80 expression reduction=(each CAM 120/80 expression rate for evaluating sample)-(LPS is individually handled
When CAM 120/80 expression rate)/when processing (no CAM 120/80 expression rate)-(CAM 120/80 when LPS is individually handled
Expression rate) } × 100 formula (1)
In addition, when to using Pg-LPS to calculate the inhibiting rate of CAM 120/80 expression reduction as LPS evaluation sample,
Use the CAM 120/80 expression rate of control group during independent addition Pg-LPS；To being commented using E.coli-LPS as LPS
When valency sample calculates the inhibiting rate of CAM 120/80 expression reduction, glued using the E- calcium of independent addition E.coli-LPS control group
Protein expression rate.
The adding ingredient and its addition used in each processing example has been recorded in the column of adding ingredient one of 1~table of table 4.Specifically
In ground, the column of adding ingredient one, while illustrating LPS species and amount, the compound used as (A) composition and its in the sample
Concentration (quality %) and the compound that is used as (B) composition and its concentration (quality %) in the sample, the addition of table 5
Species and amount that LPS is illustrated in the column of composition one, the comparative compound (ascorbic acid used instead of (A) composition and (B) composition
Sodium, Sodium Hyaluronate, sodium azulenesulfonate and menthol) and its concentration (quality %) in the sample.
[evaluation test example 2] barrier function evaluation test
In the upper strata inoculation Human gingival epithelial cells strain of culture plug-in unit (Millipore), using basal medium Humedia-KG2
Culture makes the epithelial cell membrane for showing epithelial barrier function, then removes culture medium, independent addition is respectively adopted to converging
0.01 mass % Pg-LPS culture mediums and in also added according to table beyond 0.01 mass % Pg-LPS it is described
(A) composition that is selected from of amount (is selected from the magnesium salts of tocopherol acetate, chlorophyll copper sodium, lysozyme chloride and ascorbic acid phosphoric acid esters
One or more of), (B) composition (be selected from menthones, carvol, cineole, limonene, anethole, eugenol, menthol
One or more of with cinnamic acid) and table 5 described in comparative compound (be selected from sodium ascorbate, Sodium Hyaluronate, Azulene sulphur
One or more of sour sodium and menthol) more than one culture medium, cultivate three days.After culture, remove cleaning upper strata and
The culture medium of lower floor, carries out the barrier function evaluation of epithelial cell membrane.As barrier function evaluation, the toxin from bacterium is carried out
LPS (P.g-LPS) through experiment, bacterium (gentle streptococcus (Streptcoccus mitis) (S.m bacterium)) through experiment, on
Resistance value (TER) determination experiment of chrotoplast film.
Herein, it is known that LPS is the pathogenic agent from bacterium, forms colloid in aqueous, is deposited as giant molecule
.It is known that S.m bacterium are often to occupy the bacterium in oral mucosa, it is known that its usual pathogenicity is low, but in epithelial barrier function
Purulent inflammation can be triggered during reduction.It is known that the barrier function of TER and cellular layer has very strong correlation, mainly
It is close with associating for the permeability of moisture or ion, in cosmetic field, it was reported that if TER value increases, skin
Sensation raising of moistening etc..
(Pg-LPS's passes through experiment)
Epithelial cell membrane after for cultivating three days, adds 0.2mL addition Pg-LPS on upper strata respectively and is adjusted to
0.01% Humedia-KG2,0.9mL Humedia-KG2 is added in lower floor.It is (biochemical using Pyrochrome after 4 hours
Learn industry) the P.g-LPS concentration in lower floor is quantified, barrier function is calculated by following formula (2) using the quantitative values, as a result
Represent in table 1~5 (LPS concentration, the barrier function to LPS in lower floor).
(the passing through experiment of S.m bacterium)
Epithelial cell membrane after for cultivating three days, adds being removed from Humedia-KG2 culture mediums for 0.2mL on upper strata respectively
Go suspended in the culture medium after antibiotic there are S.m bacterium and be adjusted to 107Cell/mL culture medium, in lower floor's addition
The 0.9mL culture medium without S.m bacterium.After 4 hours, sample 20 μ L from lower floor, is suitably diluted, and is inoculated into soybean pancreas egg
In white enzyme (tryptic soy) agar medium.Culture medium after inoculation is cultivated 48 hours under 37 DEG C of aerobic conditions, is based on
The clump count and dilution rate of culture medium calculate the bacteria concentration (CFU/mL) in lower floor, and represent in 1~table of table 5.Further,
Using the bacteria concentration in the lower floor, the barrier function to bacterium is calculated by following formula (2), and represent in 1~table of table 5.
(TER measure)
The value (Ω) measured using Millicell-ERS voltohmysts is multiplied by cellular layer area (cm2), calculate TER (Ω
cm2).Further, pass through following formula (2) calculating to the barrier function of ion moisture using the TER values, as a result represent in table 1
In~table 5.
[number 2]
Each barrier function=and (value when Pg-LPS is individually handled)-(evaluating value during sample treatment)/(Pg-LPS is individually handled
When value)-when processing (no value) × 100 formula (2)
In addition, though the preparation method of the evaluation sample of this evaluation test example is different from evaluation test example 1, but because culture
The adding ingredient and its amount added in base is corresponding with the adding ingredient of evaluation test example 1, so for evaluation test example 1
Adding ingredient identical evaluation test example, records the result of this evaluation test example in the lump at corresponding processing example.
[table 1]
[table 2]
[table 3]
[table 4]
[table 5]
Table 5
[result is with investigating]
(on cadherin expression rate)
As shown in Table, compared to the sample for being only added with LPS, (ascorbic acid phosphoric acid esters and its salt, life are selected from containing (A) composition
Educate phenol acetic acid esters, copper chlorophyll and its at least one of salt and lysozyme chloride) as the processing example 1~76 of adding ingredient
In, CAM 120/80 expression rate is higher, and the inhibiting rate of CAM 120/80 expression reduction is more than 9.1%.Especially, (A) into
In the processing example 6~17,19,25~36,38,44~55,57,63~74,76 for also further containing (B) composition beyond point, E-
Cadherin expression rate is more than 90%, and the inhibiting rate of CAM 120/80 expression reduction is more than 69.7%.
On the other hand, compared to the sample for being only added with LPS, the processing example handled using the adding ingredient without (A) composition
In 77~80, the reduction of CAM 120/80 expression rate, the inhibiting rate of CAM 120/80 expression reduction is negative value, it is impossible to suppress expression drop
It is low.
From the foregoing, it will be observed that according to the present invention, due to improving CAM 120/80 expression rate, CAM 120/80 reinforcing effect can be shown
Really.In addition understand, in the example that (B) composition is also contained while containing (A) composition, because CAM 120/80 expression rate becomes
Height, is more highly preferred in terms of performance CAM 120/80 reinforcing effect.
(on barrier function)
As shown in Table：
Compared to the sample without processing, (ascorbic acid phosphoric acid esters and its salt, tocopherol acetate, chlorophyll are selected from containing (A) composition
Copper and its at least one of salt and lysozyme chloride) as in the processing example 1~76 of adding ingredient, to bacterium, ion, water
The barrier function divided is higher.Especially, beyond (A) composition also further containing (B) composition processing example 6~17,19,25~
36th, it is high to the barrier function of LPS, bacterium, ion moisture in 38,44~55,57,63~74,76.
On the other hand, compared to the sample entirely without processing, the processing example 77 handled using the adding ingredient without (A) composition
It is relatively low to the barrier function of LPS, bacterium, ion moisture in~80.
From the foregoing, it will be observed that according to the present invention, it is high to the barrier function of LPS, bacterium, ion, moisture.In addition understand, containing (A) into
It is especially high thus excellent to the barrier function of LPS, bacterium, ion, moisture in processing example while dividing also containing (B) composition
Choosing.
[Formulation Example]
In formula as follows, the reinforcing effect with embodiment identical barrier function is also confirmed.
Formulation Example 1
(1) skin uses (quality %)
Formulation Example 2
(2) skin uses (quality %)
Formulation Example 3
(3) mucous epithelium uses (quality %)
Formulation Example 4
(4) mucous epithelium uses (quality %)
Formulation Example 5
(5) oral epithelium uses (quality %)
Formulation Example 6
(6) oral epithelium uses (quality %)
Formulation Example 7
(7) gingival epithelium uses (quality %)
Formulation Example 8
(8) gingival epithelium uses (quality %)
Formulation Example 9
(9) gingival epithelium uses (quality %)
Claims (21)
1. one kind is adhesively joined function intensified dose, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E
And its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
2. hardening agent according to claim 1, it is the hardening agent of mucous epithelium.
3. hardening agent according to claim 1, it is the hardening agent of oral epithelium.
4. hardening agent according to claim 1, it is the hardening agent of gingival epithelium.
5. a kind of CAM 120/80 hardening agent, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E and
Its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
6. hardening agent according to claim 5, it is the hardening agent of mucous epithelium.
7. hardening agent according to claim 5, it is the hardening agent of oral epithelium.
8. hardening agent according to claim 5, it is the hardening agent of gingival epithelium.
9. a kind of iuntercellular adhesion hardening agent, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E
And its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
10. hardening agent according to claim 9, it is the hardening agent of mucous epithelium.
11. hardening agent according to claim 9, it is the hardening agent of oral epithelium.
12. hardening agent according to claim 9, it is the hardening agent of gingival epithelium.
13. a kind of function intensified dose of epithelial barrier, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E
And its derivative, copper chlorophyll and its at least one of salt and lysozyme chloride.
14. hardening agent according to claim 13, it is the hardening agent of mucous epithelium.
15. hardening agent according to claim 13, it is the hardening agent of oral epithelium.
16. hardening agent according to claim 13, it is the hardening agent of gingival epithelium.
17. a species resistance hardening agent, it is characterised in that containing selected from ascorbic acid phosphoric acid esters and its salt, vitamin E and its spreading out
Biological, copper chlorophyll and its at least one of salt and lysozyme chloride.
18. hardening agent according to claim 17, it is the hardening agent of mucous epithelium.
19. hardening agent according to claim 17, it is the hardening agent of oral epithelium.
20. hardening agent according to claim 17, it is the hardening agent of gingival epithelium.
21. the hardening agent according to any one of claim 1~20, it, which also contains, is selected from menthones, carvol, eucalyptus
It is more than one or both of brain, limonene, anethole, eugenol, menthol and cinnamic acid.
Priority Applications (1)
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| CN202010607375.XA CN111658640A (en) | 2014-12-24 | 2015-12-22 | Adhesion bonding functional enhancer |
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| PCT/JP2015/085867 WO2016104524A1 (en) | 2014-12-24 | 2015-12-22 | Agent for enhancing adherens junction function |
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| JP (1) | JP6755185B2 (en) |
| KR (1) | KR20170097013A (en) |
| CN (2) | CN107106539A (en) |
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| JP7412869B2 (en) * | 2016-08-05 | 2024-01-15 | 小林製薬株式会社 | Gum care agent and oral composition for gum care containing the same |
| JP7237465B2 (en) * | 2018-05-25 | 2023-03-13 | ポーラ化成工業株式会社 | A screening method using the expression levels of the occludin gene, the claudin gene, and the zo-1 gene under hypoxic conditions as an indicator, an inhibitor of claudin gene expression reduction, an inhibitor of cell adhesion apparatus function deterioration, and a reduction in skin barrier function ameliorating or preventive agent |
| WO2019225728A1 (en) * | 2018-05-25 | 2019-11-28 | ポーラ化成工業株式会社 | Method for screening for components that improve condition of aged or hypoxic skin, and method for estimating oxygen level of subdermal tissue or fibrosis level of subdermal adipocytes as index of subdermal tissue viscoelasticity |
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| US6093706A (en) * | 1992-03-04 | 2000-07-25 | Bioresponse, L.L.C. | Combined dehydroepiandrosterone and retinoid therapy for epithelial disorders |
| US20100015119A1 (en) * | 2007-03-13 | 2010-01-21 | Haruzo Kobayashi | Epithelium-improving agent |
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| JPH10236935A (en) * | 1996-08-02 | 1998-09-08 | Kao Corp | Oral solid preparation |
| JP2001055318A (en) * | 1999-08-17 | 2001-02-27 | Lion Corp | Composition for oral cavity |
| EP2046274A1 (en) * | 2006-08-02 | 2009-04-15 | Wm. Wrigley Jr. Company | Oral compositions effective for the treatment of oral cavity malodor associated with the consumption of odor-causing compounds |
| CA2896646A1 (en) * | 2012-12-27 | 2014-07-03 | Hayashibara Co., Ltd. | Skin-exterior anti-ageing composition and production method therefor |
| CN103641837B (en) * | 2013-11-15 | 2016-03-23 | 云南瑞宝生物科技股份有限公司 | A kind of method of chlorophyll copper sodium extracting from silkworm excrement |
| CN103751031A (en) * | 2014-01-09 | 2014-04-30 | 广州市科玮生物技术有限公司 | Mouthwash containing antimicrobial peptide and sodium copper chlorophyllin and preparation method of mouthwash |
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2015
- 2015-12-22 CN CN201580071316.2A patent/CN107106539A/en active Pending
- 2015-12-22 CN CN202010607375.XA patent/CN111658640A/en active Pending
- 2015-12-22 KR KR1020177013772A patent/KR20170097013A/en not_active Application Discontinuation
- 2015-12-22 MY MYPI2017702182A patent/MY186939A/en unknown
- 2015-12-22 WO PCT/JP2015/085867 patent/WO2016104524A1/en active Application Filing
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|---|---|---|---|---|
| US6093706A (en) * | 1992-03-04 | 2000-07-25 | Bioresponse, L.L.C. | Combined dehydroepiandrosterone and retinoid therapy for epithelial disorders |
| US20100015119A1 (en) * | 2007-03-13 | 2010-01-21 | Haruzo Kobayashi | Epithelium-improving agent |
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| Publication number | Publication date |
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| CN111658640A (en) | 2020-09-15 |
| MY186939A (en) | 2021-08-26 |
| WO2016104524A1 (en) | 2016-06-30 |
| KR20170097013A (en) | 2017-08-25 |
| JPWO2016104524A1 (en) | 2017-10-05 |
| JP6755185B2 (en) | 2020-09-16 |
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