WO2011102529A1 - 上皮細胞間接着増強剤およびこれを用いたアレルギー改善、治療または予防剤 - Google Patents
上皮細胞間接着増強剤およびこれを用いたアレルギー改善、治療または予防剤 Download PDFInfo
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- WO2011102529A1 WO2011102529A1 PCT/JP2011/053833 JP2011053833W WO2011102529A1 WO 2011102529 A1 WO2011102529 A1 WO 2011102529A1 JP 2011053833 W JP2011053833 W JP 2011053833W WO 2011102529 A1 WO2011102529 A1 WO 2011102529A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to an epithelial cell adhesion enhancer and an allergy ameliorating, treating or preventing agent using the same, and in particular, by enhancing cell-cell adhesion (epithelial cell adhesion) of epithelial cells, which is one of barrier functions against allergens.
- the present invention relates to an epithelial cell adhesion enhancer capable of improving, treating and preventing allergy, and an allergy improving, treating or preventing agent using the same.
- the organs that come into contact with foreign bodies in the human body are the epidermis, respiratory organs, and digestive organs.
- the digestive organ has a unique immune system, and has recently attracted attention as an immune organ that greatly affects the immune system of the whole body.
- the mainstream method is to improve the compositional balance of the intestinal flora based on the fact that the intestinal bifidobacteria of children with allergies are less than that of healthy children.
- Patent Document 1 describes a method using an allergy-preventing agent containing fructooligosaccharides. ing. JP 2003-201239 (Patent Document 2) describes an immunostimulatory food containing fructooligosaccharides.
- Patent Document 3 describes Japanese Patent Application Laid-Open No. 2008-280354 (Patent Document 4) describe methods for suppressing allergy.
- Patent Document 1 describes a method of ingesting a composition containing a magnesium source, fructooligosaccharides and indigestible sugar alcohols against allergy hate due to magnesium deficiency.
- intestinal bacteria produce organic acids with fructooligosaccharides, and this organic acid and indigestible sugar alcohol promotes magnesium absorption to prevent allergic disappointment.
- Patent Document 2 describes a method of inducing intestinal immunity by inducing IgA production from Peyer's patches by ingesting fructooligosaccharides. However, this method is very effective and very difficult to take every day.
- Patent Document 3 contains an allergy inhibitor as a first composition having a maximum composition ratio of 1-kestose in fructooligosaccharide
- Patent Document 4 contains 1-kestose as a first composition in fructooligosaccharide as a first composition ratio.
- Each of the allergy-suppressing oligosaccharides described is described.
- These allergy-suppressing agents and allergy-suppressing oligosaccharides have a high allergy-suppressing effect as compared with the allergic effects described in Patent Documents 1 and 2.
- Clinical effects of kestose, a prebiotic oligosaccharide, on thetreme of atopic dermatitis in infants. also reports that as a result of an intake test of 1-kestose for infants, there is no strong correlation between improvement of allergic symptoms and growth of bifidobacteria.
- Non-patent Documents 2 and 3 cysteine / serine protease activity commonly possessed by substances that can be allergens degrades tight junction proteins between epithelial cells and weakens adhesion between epithelial cells. Therefore, the idea is to improve, treat or prevent allergies by repairing or promoting the formation of tight junction proteins between epithelial cells, thereby enhancing the adhesion between epithelial cells and suppressing the entry of allergens into the body. A method based on has been tried.
- Patent Document 5 a fish white or yeast-derived nucleic acid
- Patent Document 6 a cellulase preparation-derived peptide
- Patent Literature 7 monoacylganglioside 3
- Patent Literature 8 lipoteichoic acid derived from lactic acid bacteria
- Patent Literature 9 whey protein
- Patent Documents 5 to 8 have a complicated production process, and industrial mass production is very difficult.
- the substance of patent document 9 is easy to produce, since it must be ingested in large quantities in order to acquire an effect, it is difficult to ingest every day. For these reasons, a preparation capable of improving, treating or preventing allergy caused by the above substances has not been realized.
- JP-A-8-157379 JP 2003-201239 A Japanese Patent No. 4162147 JP 2008-280354 A Japanese Patent No. 4050799 JP 2002-275196 A Japanese Patent No. 4034364 Japanese Patent Laid-Open No. 2008-212006 Japanese Patent No. 4330088
- the present invention is based on the idea of improving, treating or preventing allergy by enhancing adhesion between epithelial cells and suppressing invasion of allergens into the body.
- the present inventors have found that a combination of a divalent metal cation and a specific oligosaccharide further enhances adhesion between epithelial cells even when compared to a divalent metal cation.
- the present invention is generally familiar as oligosaccharides are foods, divalent metal cations are present in the living body, and are not toxic to the living body within a physiological concentration range. Nonetheless, a composition comprising a specific oligosaccharide and a divalent metal cation that is very safe and effective compared to synthetic oral steroids and is effective in allergy improvement, treatment or prevention, or local inflammatory response
- the purpose is to provide goods.
- the agent for enhancing adhesion between cells in epithelial cells comprising 1-kestose and / or nystose and a divalent metal cation as active ingredients.
- 1-kestose is a 1-kestose-containing oligosaccharide having a purity of 95% by weight or more, and the divalent metal cation is 1 part by weight or more with respect to 10 parts by weight of the 1-kestose-containing oligosaccharide.
- the agent according to (2) is a 1-kestose-containing oligosaccharide having a purity of 95% by weight or more, and the divalent metal cation is 1 part by weight or more with respect to 10 parts by weight of the 1-kestose-containing oligosaccharide.
- the epithelial cell adhesion enhancing agent and the allergy ameliorating, treating or preventing agent using the same in addition to suppressing the destruction of the epithelial tight junction protein that causes the allergen to enter the body, the epithelium By repairing or promoting the formation of an intercellular tight junction protein, it is possible to enhance the adhesion between epithelial cells and effectively improve, treat and prevent allergic symptoms.
- Example 1 it is a figure which shows the result of having measured the time-dependent change of TEER by 1-kestose and nystose addition.
- Example 2 it is a figure which shows the result of having measured the time-dependent change of TEER by 1-kestose addition.
- Example 3 it is a figure which shows the result of having measured the time-dependent change of TEER by 1-kestose addition.
- Example 4 it is a figure which shows the result of having measured the time-dependent change of TEER by 1-kestose addition.
- Example 4 it is a figure which shows the result of having measured the time-dependent change of TEER by 1-kestose addition.
- Example 5 it is a figure which shows the result of having measured the change of the substance permeation
- Example 6 it is a figure which shows the result of having measured the change of TEER by 1-kestose addition.
- the epithelial cell adhesion enhancer according to the present invention is an intercellular adhesion enhancer in epithelial cells, and contains 1-kestose and / or nystose and a divalent metal cation, or 1-kestose and a divalent metal cation.
- the active ingredient is 1-kestose and / or nystose and a divalent metal cation, or 1-kestose and a divalent metal cation.
- Non-patent Documents 2 and 3 Non-patent Documents 2 and 3
- the agent for enhancing adhesion between epithelial cells according to the present invention repairs or promotes the formation of tight junction proteins between epithelial cells, thereby enhancing the adhesion between epithelial cells and suppressing the entry of allergens into the body.
- the epithelial cell adhesion enhancing agent and the allergy improving, treating or preventing agent using the same according to the present invention can improve, treat or prevent allergies.
- the epithelial cells include, for example, absorptive epithelial cells, keratinized epithelial cells, wet stratified barrier epithelial cells (wet-stabilized barrier epithelium), inner lining epithelial cells (lining epithelium), exocrine epithelial cells, endocrine epithelial cells, Examples include extracellular matrix secretory epithelial cells and contractile epithelial cells.
- intestinal epithelial cells such as small intestinal epithelial cells, large intestine epithelial cells, and duodenal epithelial cells, gastric mucosal epithelial cells, esophageal epithelial cells, cornea
- intestinal epithelial cells such as small intestinal epithelial cells, large intestine epithelial cells, and duodenal epithelial cells
- gastric mucosal epithelial cells gastric mucosal epithelial cells
- esophageal epithelial cells esophageal epithelial cells
- cornea examples include epithelial cells, conjunctival epithelial cells, amniotic epithelial cells, skin epithelial cells, palatal epithelial cells, and the like.
- the divalent metal cation may be any divalent metal cation that is present in the living body and has no toxicity to the living body within the range of physiological concentrations.
- divalent metal cation such as barium ions, iron ions, copper ions, and zinc ions can be mentioned.
- calcium ions are used as a suitable divalent metal cation.
- examples of the oligosaccharide that can be used include fructooligosaccharides such as 1-kestose, nystose, and fructosyl nystose excluding sucrose.
- 1-kestose or nystose is used as a suitable oligosaccharide.
- 1-kestose is a fructotrisaccharide composed of one molecule of glucose residue and two molecules of fructose residue.
- 1-kestose that can be used in the present invention, for example, after being prepared by an enzymatic reaction using sucrose as a raw material, monosaccharides and sucrose are removed by chromatographic separation, and the purity thereof is reduced.
- a 1-kestose-containing oligosaccharide having a purity of 95% by weight or more, which has been enhanced and produced by a crystallization method, can be mentioned.
- Such 1-kestose-containing oligosaccharides are excellent in solubility, indigestible and low energy substances. Furthermore, it has an IgA production enhancing action and an IgE production inhibiting action (Patent Documents 3 and 4).
- Japanese Patent Application Laid-Open No. 58-201980 discloses the method of increasing the purity by using a monosaccharide or sucrose using a chromatographic separation method.
- the methods described in Japanese Patent Application No. 11-34787 Japanese Patent Laid-Open No. 2000-2328778 and the crystal method described in Japanese Patent Application No. 2-24312 (Japanese Patent Laid-Open No. 4-235192) can be used.
- the contents of Japanese Patent Application No. 11-34787, Japanese Patent Application No. 2-24312, Japanese Patent Application No. 2005-371005 (Cited Document 3) and Japanese Patent Application No. 2008-166463 (Cited Document 4) are included in this specification.
- the daily intake of 1-kestose in the present invention is preferably 0.015 g / kg body weight or more.
- 1 part by weight of divalent metal ions is 10 parts by weight of 1-kestose.
- conversion about 2.5 g is preferable.
- the adhesion between epithelial cells in the present invention is achieved by repairing or promoting formation of an epithelial cell tight junction protein.
- “enhancement” is used interchangeably with “activation”, “promotion”, “strengthening”, “promotion”, and the like.
- allergies examples include atopy, allergic rhinitis, allergic conjunctivitis, allergic gastroenteritis, bronchial asthma, childhood asthma, urticaria, animal allergies, food allergies, metal allergies, drug allergies, anaphylaxis, etc.
- the dosage form may also be a dosage form that can be appropriately selected by those skilled in the art.
- examples of such a dosage form include tablets, granules, powders, capsules, and coating agents in the case of preparation as an oral dosage formulation.
- forms such as inhalants, injections, drops, suppositories, coating agents, sprays, patches etc.
- the dosage can be appropriately set depending on the formulation form of the pharmaceutical composition, the administration method, the purpose of use, and the age, weight and symptom of the administration subject applied thereto.
- the epithelial cell adhesion enhancing agent according to the present invention and the allergy improving, treating or preventing agent using the same will be described based on examples. Note that the technical scope of the present invention is not limited to the features shown by these examples.
- Example 1 Experiment to confirm the effect of 1-kestose promoting the recovery from the decrease in adhesion between epithelial cells due to extracellular calcium deficiency
- Example 1 the effect of 1-kestose promoting the recovery from decreased adhesion between epithelial cells due to extracellular calcium deficiency was confirmed by experiments using cultured cells.
- the composition of the 1-kestose-containing oligosaccharide used in Example 1 is such that 1-kestose is 98% by weight, nystose is 1% by weight, and sucrose is 1% by weight, that is, the purity of 1-kestose is 1%. 98% by weight oligosaccharides.
- the electrical resistance between epithelial cells (TEER) was used as a parameter
- Colon epithelial cancer cells Caco-2 cells were subcultured in DMEM medium (GIBCO) containing 10% FBS, and the cultured cells of the 48th generation were cryopreserved and used for the subsequent experiments.
- Caco-2 cells were seeded on the upper layer of a transwell (Corning Life Science) and cultured in a DMEM medium containing 10% FBS in a 5% CO 2 , 37 ° C. incubator. The cells were cultured until the electrical resistance (TEER) between the upper layer and the lower layer of the transwell reached 400 to 500 ⁇ ⁇ cm 2 .
- TEER electrical resistance
- Example 1 the measurement result of the TEER ratio in Example 1 is shown in FIG.
- the negative control group almost no TEER recovery was observed, but in the 1% kestose group, 1% nystose group, and positive control group, significant TEER recovery was observed compared to the negative control group.
- the 1% kestose group and the 1% nystose group showed a significant recovery promoting effect compared to the positive control group.
- the 1% kestose group 30 minutes after replacing the calcium-deficient DMEM medium with the calcium-containing DMEM medium, an average 2.4-fold recovery promoting effect was observed compared to the positive control group.
- the 1% kestose group showed a stronger tendency to promote recovery. As a result, it was confirmed that 1-kestose has a strong recovery promoting action on the decreased adhesion between epithelial cells.
- Example 2 Experiment for confirming that the effect of 1-kestose promoting the recovery from reduced adhesion between epithelial cells due to extracellular calcium deficiency is calcium-dependent]
- Example 2 it was confirmed by an experiment using cultured cells that the effect of promoting the recovery from the decrease in adhesion between epithelial cells due to extracellular calcium deficiency exhibited by 1-kestose occurs in a calcium-dependent manner.
- the 1-kestose-containing oligosaccharide was of the same purity used in Example 1, and the culture conditions of the cultured cells were the same as in Example 1.
- Example 2 the measurement result of the TEER ratio in Example 2 is shown in FIG.
- the negative control group and the calcium ( ⁇ ) 1% kestose group almost no TEER recovery was observed.
- Example 1 a significant recovery of TEER was observed in the calcium (+) 1% kestose group and the positive control group, and in the calcium (+) 1% kestose group, the positive control group was also improved.
- Example 1 a significant recovery promoting effect of TEER was observed.
- 1-kestose does not show the recovery effect of TEER in the absence of extracellular calcium, and the recovery promoting effect of the decreased adhesion between epithelial cells caused by 1-kestose occurs dependent on extracellular calcium. .
- Example 3 Experiment for confirming that concentration-dependent effect of 1-kestose promoting the recovery from decreased adhesion between epithelial cells due to extracellular calcium deficiency]
- Example 3 it was confirmed by an experiment using cultured cells that the effect of promoting recovery from a decrease in adhesion between epithelial cells due to extracellular calcium deficiency exhibited by 1-kestose occurred in a concentration-dependent manner.
- the 1-kestose-containing oligosaccharide was of the same purity used in Example 1, and the culture conditions of the cultured cells were the same as in Example 1.
- Example 3 the measurement result of the TEER ratio in Example 3 is shown in FIG. Similar to Example 1, almost no recovery of TEER was observed in the negative control group. However, significant recovery of TEER was seen in the 1% kestose group, 0.1% kestose group, and positive control group compared to the negative control group. The 1% kestose group showed a stronger tendency to promote TEER recovery than the 0.1% kestose group. From the above, it was confirmed that the recovery promoting effect of the decreased adhesion between epithelial cells caused by 1-kestose occurs in a concentration-dependent manner.
- Example 4 Experiment to examine the effect of pre-administration of 1-kestose to suppress the decrease in epithelial cell adhesion due to extracellular calcium deficiency. In Example 4, it was confirmed by an experiment using cultured cells whether or not administration of 1-kestose in advance could suppress a decrease in adhesion between epithelial cells due to extracellular calcium deficiency.
- the 1-kestose-containing oligosaccharide was of the same purity used in Example 1, and the culture conditions of the cultured cells were the same as in Example 1.
- FIG. 4 shows the results of comparison with the 1 hour calcium (+) 1% kestose group, the 1 hour calcium (+) negative control group, and the positive control group.
- the 1 hour calcium (+) 1% kestose group showed a significant increase in TEER compared to the 1 hour calcium (+) negative control group and the positive control group in the TEER measurement immediately before replacement with calcium deficient DMEM medium.
- the decrease in TEER in the 1 hour calcium (+) 1% kestose group tends to be suppressed compared to the 1 hour calcium (+) negative control group.
- FIG. 5 shows the results of comparison with the 6-hour calcium (+) 1% kestose group, the 6-hour calcium (+) negative control group, and the positive control group. Similar to FIG. 4, the 6-hour calcium (+) 1% kestose group was significantly compared with the 6-hour calcium (+) negative control group and the positive control group in the TEER measurement immediately before replacement with the calcium-deficient DMEM medium. An increase in TEER was observed. Similarly, when replaced with calcium-deficient DMEM medium and the oligosaccharide containing 1-kestose is removed, the decrease in TEER in the 6-hour calcium (+) 1% kestose group is suppressed compared to the 6-hour calcium (+) negative control group There was a tendency to be.
- Example 5 Experiment for confirming the permeation-suppressing effect of a substance on enhancement of cell membrane permeability due to extracellular calcium deficiency
- Example 5 the inhibitory effect of substance permeability on the enhancement of cell membrane permeability due to extracellular calcium deficiency exhibited by 1-kestose was confirmed by experiments using cultured cells, including comparison with other fructooligosaccharides.
- the 1-kestose-containing oligosaccharide was of the same purity used in Example 1, and the culture conditions of the cultured cells were the same as in Example 1.
- Caco-2 cells cultured until the TEER of the transwell becomes 400 to 500 ⁇ ⁇ cm 2 are replaced with a calcium-deficient colorless HBSS medium (GIBCO) from DMEM medium containing 10% FBS, and then cultured for 2 hours, followed by calcium-containing colorless HBSS 1-kestose-containing oligosaccharide, sucrose, or nystose is added to the upper layer in a medium (GIBCO) at a concentration of 1% by weight, and Lucifer Yellow (MPBiomedical) is added to the upper layer as an intercellular permeant at a concentration of 100 ⁇ M for 3 hours.
- GBCO calcium-deficient colorless HBSS medium
- Example 5 the measurement result of the Lucifer Yellow lower layer residual concentration in Example 5 is shown in FIG.
- a significant decrease in residual concentration was observed in the 1% kestose group, 1% nystose group, and positive control group.
- the 1% kestose group and the 1% nystose group tended to show a lower residual concentration, and the 1% kestose group tended to have the lowest residual concentration.
- 1-kestose has the effect of suppressing the permeability of allergen proteins and the like by promoting adhesion between epithelial cells.
- Example 6 Experiment to confirm the effect of suppressing the decrease in adhesion between epithelial cells by inflammatory cytokine IL-1 ⁇ ”
- Example 6 the effect of suppressing the decrease in adhesion between epithelial cells caused by the inflammatory cytokine exhibited by 1-kestose was confirmed by an experiment using cultured cells.
- the 1-kestose-containing oligosaccharide was of the same purity used in Example 1, and the culture conditions of the cultured cells were the same as in Example 1.
- ( ⁇ ), IL-1 ⁇ ( ⁇ ) group, n 3) were prepared and the TEER ratios were compared.
- Example 6 the measurement result of the TEER ratio in Example 6 is shown in FIG.
- the average TEER ratio was 0.914, and the standard deviation was 0.031
- the TEER ratio was The average value of TEER ratio was 0.849 and the standard deviation was 0.0003 in the group of 0.585, standard deviation 0.002, 1% kestose (+), and IL-1 ⁇ (+). From these results, it was shown that TEER decreased by IL-1 ⁇ was suppressed by about 26% by addition of oligosaccharide containing 1-kestose. As a result, it was confirmed that 1-kestose has an effect of suppressing a decrease in adhesion between epithelial cells due to a local inflammatory reaction.
- the present invention contributes to the improvement, treatment and prevention of allergy by repairing or promoting the formation of tight junction protein between epithelial cells, which is the cause of allergic diseases.
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Abstract
Description
(6)(1)から(5)の何れかに記載の剤を用いたアレルギー改善、治療または予防剤。
実施例1では、1-ケストースが示す細胞外カルシウム欠乏による上皮細胞間接着低下からの回復を促進する効果を、培養細胞を用いた実験により確認した。
実施例2では、1-ケストースが示す細胞外カルシウム欠乏による上皮細胞間接着低下からの回復を促進する効果がカルシウム依存的に生じることを、培養細胞を用いた実験により確認した。
実施例3では、1-ケストースが示す細胞外カルシウム欠乏による上皮細胞間接着低下からの回復を促進する効果が濃度依存的に生じることを、培養細胞を用いた実験により確認した。
実施例4では、1-ケストースを事前に投与することで細胞外カルシウム欠乏による上皮細胞間接着の低下抑制が起こりうるかを、培養細胞を用いた実験により確認した。
実施例5では、1-ケストースが示す細胞外カルシウム欠乏による細胞膜透過性亢進に対する物質透過性の抑制効果を、他のフラクトオリゴ糖との比較を含めて培養細胞を用いた実験により確認した。
実施例6では、1-ケストースが示す炎症性サイトカインによる上皮細胞間接着低下を抑制する効果を、培養細胞を用いた実験により確認した。
Claims (6)
- 上皮細胞における細胞間接着増強剤であって、1-ケストースおよび/またはニストースならびに2価の金属陽イオンを有効成分とする前記剤。
- 1-ケストースおよび2価の金属陽イオンを有効成分とする、請求項1に記載の剤。
- 1-ケストースが純度95重量%以上の1-ケストース含有オリゴ糖であって、前記1-ケストース含有オリゴ糖10重量部に対して2価の金属陽イオンが1重量部以上である、請求項2に記載の剤。
- 2価の金属陽イオンがカルシウムイオンである、請求項1から請求項3の何れかに記載の剤。
- 上皮細胞が腸管上皮細胞である、請求項1から請求項4の何れかに記載の剤。
- 請求項1から請求項5の何れかに記載の剤を用いたアレルギー改善、治療または予防剤。
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201180010498.4A CN102791274B (zh) | 2010-02-22 | 2011-02-22 | 上皮细胞间粘接增强剂和使用该增强剂的过敏的改善、治疗或预防剂 |
EP11744815.9A EP2540300B1 (en) | 2010-02-22 | 2011-02-22 | Epithelial cell-cell adhesion enhancer for use in ameliorating, treatment and prevention of allergic diseases |
CA2790783A CA2790783C (en) | 2010-02-22 | 2011-02-22 | Epithelial cell-cell adhesion enhancer, and ameliorating, therapeutic or prophylactic agent for allergic diseases using same |
JP2012500692A JPWO2011102529A1 (ja) | 2010-02-22 | 2011-02-22 | 上皮細胞間接着増強剤およびこれを用いたアレルギー改善、治療または予防剤 |
US13/580,539 US20120315342A1 (en) | 2010-02-22 | 2011-02-22 | Epithelial cell-cell adhesion enhancer, and ameliorating, therapeutic or prophylactic agent for allergic diseases using same |
ES11744815.9T ES2545749T3 (es) | 2010-02-22 | 2011-02-22 | Potenciador de la adhesión célula-célula epitelial para uso en la mejora, tratamiento y prevención de enfermedades alérgicas |
KR1020127024612A KR101833249B1 (ko) | 2010-02-22 | 2011-02-22 | 상피세포간 접착 증강제 및 이것을 이용한 알러지 질환의 개선, 치료 또는 예방제 |
HK13105341.0A HK1178433A1 (en) | 2010-02-22 | 2013-05-03 | Epithelial cell-cell adhesion enhancer, and ameliorating, therapeutic or prophylactic agent for allergic diseases using same |
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CN (1) | CN102791274B (ja) |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012176907A (ja) * | 2011-02-25 | 2012-09-13 | Glico Dairy Products Co Ltd | フラクトオリゴ糖を有効成分とするミオシン軽鎖脱リン酸化促進剤、疾患の予防又は治療剤、及び飲食品 |
JP2016148636A (ja) * | 2015-02-13 | 2016-08-18 | 学校法人兵庫医科大学 | 微粒子状物質によるアレルギー性鼻炎増悪の予防又は抑制剤 |
JP2019502668A (ja) * | 2015-12-03 | 2019-01-31 | ビトップ アクチエンゲゼルシャフトbitop AG | 上皮組織におけるバリア欠陥を伴う疾患の予防または治療において使用するための適合溶質または溶質混合物 |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012176907A (ja) * | 2011-02-25 | 2012-09-13 | Glico Dairy Products Co Ltd | フラクトオリゴ糖を有効成分とするミオシン軽鎖脱リン酸化促進剤、疾患の予防又は治療剤、及び飲食品 |
JP2016148636A (ja) * | 2015-02-13 | 2016-08-18 | 学校法人兵庫医科大学 | 微粒子状物質によるアレルギー性鼻炎増悪の予防又は抑制剤 |
JP2019502668A (ja) * | 2015-12-03 | 2019-01-31 | ビトップ アクチエンゲゼルシャフトbitop AG | 上皮組織におけるバリア欠陥を伴う疾患の予防または治療において使用するための適合溶質または溶質混合物 |
JP2021169540A (ja) * | 2015-12-03 | 2021-10-28 | ビトップ アクチエンゲゼルシャフトbitop AG | 上皮組織におけるバリア欠陥を伴う疾患の予防または治療において使用するための適合溶質または溶質混合物 |
JP7397830B2 (ja) | 2015-12-03 | 2023-12-13 | ビトップ アクチエンゲゼルシャフト | 上皮組織におけるバリア欠陥を伴う疾患の予防または治療において使用するための適合溶質または溶質混合物 |
Also Published As
Publication number | Publication date |
---|---|
EP2540300B1 (en) | 2015-07-15 |
JPWO2011102529A1 (ja) | 2013-06-17 |
CA2790783C (en) | 2018-07-03 |
US20120315342A1 (en) | 2012-12-13 |
EP2540300A1 (en) | 2013-01-02 |
KR20130043614A (ko) | 2013-04-30 |
KR101833249B1 (ko) | 2018-02-28 |
ES2545749T3 (es) | 2015-09-15 |
CA2790783A1 (en) | 2011-08-25 |
CN102791274B (zh) | 2015-08-26 |
HK1178433A1 (en) | 2013-09-13 |
EP2540300A4 (en) | 2013-08-14 |
CN102791274A (zh) | 2012-11-21 |
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