JP2024014191A - Composition for reducing activity of egg allergen - Google Patents
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本開示は、卵アレルゲン活性低減用組成物等に関する。 The present disclosure relates to a composition for reducing egg allergen activity and the like.
近年、アトピー性皮膚炎、気管支喘息、アレルギー性鼻炎など多くのアレルギー疾患が問題となってきている。アレルギー疾患は、例えばアレルゲンを含有する食物を摂取することで生じるもの（食物アレルギー）の他、環境中（例えば大気中や住居）に存在するアレルゲンによって引き起こされる場合もある。より具体的には、例えば、大気中に存在するアレルゲンを吸入したり、あるいは住居空間に存在する物体（ドアや壁など）に存在するアレルゲンに触れるなどして、生じる場合もある。このため、環境中のアレルゲンの除去や活性低減化も重要であると考えられている。これまでに、環境中のアレルゲン活性を低減するために、例えば、ダニアレルゲンや花粉アレルゲンに対してその活性を低減する作用を有する製剤が開発されてきた（特許文献１～５）。しかしながら、食物アレルゲンについては、そもそも環境中に存在するという認識が薄く、特に食物アレルゲンの１つである卵アレルゲンの活性を低減する作用を有する成分についてはほとんど報告がなかった。このため、卵アレルゲン（特に環境中に存在する卵アレルゲン）の活性を低減する方法の開発が望まれていた。 In recent years, many allergic diseases such as atopic dermatitis, bronchial asthma, and allergic rhinitis have become a problem. Allergic diseases can be caused, for example, by ingesting food containing allergens (food allergy), or can be caused by allergens present in the environment (for example, in the air or in your home). More specifically, it can occur, for example, by inhaling allergens present in the air, or by touching allergens present on objects (doors, walls, etc.) in a residential space. For this reason, it is considered important to remove allergens in the environment and reduce their activity. To date, in order to reduce the activity of allergens in the environment, for example, preparations that have the effect of reducing the activity of mite allergens and pollen allergens have been developed (Patent Documents 1 to 5). However, with regard to food allergens, there is little recognition that they exist in the environment in the first place, and in particular, there have been few reports on ingredients that have the effect of reducing the activity of egg allergen, which is one of the food allergens. Therefore, it has been desired to develop a method for reducing the activity of egg allergens (particularly egg allergens present in the environment).
本開示は、卵アレルゲン（特に環境中に存在する卵アレルゲン）の活性を低減する組成物を提供することを課題とする。 An object of the present disclosure is to provide a composition that reduces the activity of egg allergens (particularly egg allergens present in the environment).
本発明者らは、ヨウ化ポリビニルピロリドンが卵アレルゲンの活性を低減することを見出し、さらに改良を重ねた。 The present inventors discovered that polyvinylpyrrolidone iodide reduces the activity of egg allergens, and made further improvements.
本開示は、例えば以下の項に記載の主題を包含する。
項１．
ヨウ化ポリビニルピロリドンを含む、卵アレルゲン活性低減用組成物。
項２．
ヨウ化ポリビニルピロリドンを０．０１質量％以上含有する、項１に記載の組成物。
項３．
前記卵アレルゲンが、卵白アレルゲンである、項１又は２に記載の組成物。
項４．
前記卵アレルゲンが、オボアルブミンである、項１又は２に記載の組成物。
項５．
前記卵アレルゲンが、環境中の卵アレルゲンである、項１～４のいずれかに記載の組成物。
The present disclosure encompasses, for example, the subject matter described in the following sections.
Item 1.
A composition for reducing egg allergen activity containing polyvinylpyrrolidone iodide.
Item 2.
Item 2. The composition according to item 1, containing 0.01% by mass or more of polyvinylpyrrolidone iodide.
Item 3.
Item 3. The composition according to item 1 or 2, wherein the egg allergen is an egg white allergen.
Item 4.
Item 3. The composition according to item 1 or 2, wherein the egg allergen is ovalbumin.
Item 5.
5. The composition according to any one of items 1 to 4, wherein the egg allergen is an environmental egg allergen.
卵アレルゲンの活性を低減することができる。 The activity of egg allergens can be reduced.
以下、本開示に包含される各実施形態について、さらに詳細に説明する。
本開示に包含される組成物は、ヨウ化ポリビニルピロリドンを含む。本明細書において、当該組成物を「本開示の組成物」と表記することがある。
Each embodiment included in the present disclosure will be described in further detail below.
Compositions encompassed by this disclosure include polyvinylpyrrolidone iodide. In this specification, the composition may be referred to as "composition of the present disclosure."
ヨウ化ポリビニルピロリドン（ｐｏｖｉｄｏｎｅ ｉｏｄｉｎｅ；ＰＶＰ－Ｉ）とは、１－ビニル－２－ピロリドンの重合物（ポリビニルピロリドン）とヨウ素の複合体であり、ポビドンヨードとも称される。ヨウ化ポリビニルピロリドンは、うがい薬や手指の殺菌、傷の消毒薬などに広く使われている代表的な消毒剤であり、よって安全性にも優れている。 Polyvinylpyrrolidone iodide (PVP-I) is a complex of a polymer of 1-vinyl-2-pyrrolidone (polyvinylpyrrolidone) and iodine, and is also called povidone iodine. Polyvinylpyrrolidone iodide is a typical disinfectant widely used in mouthwashes, hand disinfectants, wound disinfectants, etc., and is therefore extremely safe.
本開示の組成物に含まれるヨウ化ポリビニルピロリドンの含有量は、卵アレルゲンの活性を低減し得る限り特に限定されない。例えば、０．０１質量％以上とすることができる。当該範囲の上限若しくは下限は、例えば、０．０１５、０．０２、０．０４、０．０６、０．０８、０．１、０．１２、０．１４、０．１６、０．１８、０．２、０．３、０．４、又は０．５質量％程度であってもよい。より具体的には、例えば、０．０１～０．２質量％程度であってもよく、０．０２～０．１質量％程度であってもよい。 The content of polyvinylpyrrolidone iodide contained in the composition of the present disclosure is not particularly limited as long as it can reduce the activity of egg allergens. For example, it can be 0.01% by mass or more. The upper limit or lower limit of the range is, for example, 0.015, 0.02, 0.04, 0.06, 0.08, 0.1, 0.12, 0.14, 0.16, 0.18, It may be about 0.2, 0.3, 0.4, or 0.5% by mass. More specifically, for example, it may be about 0.01 to 0.2% by mass, or about 0.02 to 0.1% by mass.
本開示の組成物は、後述する実施例に示すとおり、卵アレルゲンの活性を低減することができる。卵アレルゲンとしては、例えば、卵白アレルゲン、卵黄アレルゲン等が挙げられる。中でも、卵白アレルゲンが好ましい。卵白アレルゲンとしては、例えば、オボアルブミン、オボムコイド、リゾチーム、オボトランスフェリン等が挙げられる。中でも、オボアルブミンが好ましい。対象とする卵アレルゲンは、１種単独であってもよく、２種以上を組み合わせであってもよい。
また、近年、卵アレルゲンは、環境中に存在していることが報告されている。このため、本開示の組成物は、環境中の卵アレルゲンの活性低減用として好適に用いることができる。
The composition of the present disclosure can reduce the activity of egg allergens, as shown in the Examples below. Examples of egg allergens include egg white allergen and egg yolk allergen. Among these, egg white allergen is preferred. Examples of egg white allergens include ovalbumin, ovomucoid, lysozyme, and ovotransferrin. Among them, ovalbumin is preferred. The target egg allergen may be one type alone or a combination of two or more types.
Furthermore, in recent years, it has been reported that egg allergens exist in the environment. Therefore, the composition of the present disclosure can be suitably used for reducing the activity of egg allergens in the environment.
本開示の組成物は、ヨウ化ポリビニルピロリドンを含み、さらに他の成分を含むことができる。当該他の成分としては、例えば、溶剤、担体、分散剤、乳化剤、緩衝剤、安定剤、賦形剤、結合剤、崩壊剤、滑沢剤、増粘剤、界面活性剤、抗酸化剤、保存剤、防腐剤、除菌剤、コーティング剤、着色料、香料、ｐＨ調整剤、その他の抗アレルゲン成分等が例示される。これらの成分は、１種単独で又は２種以上を組み合わせて用いることができる。 Compositions of the present disclosure include polyvinylpyrrolidone iodide and may further include other ingredients. Examples of the other components include solvents, carriers, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, thickeners, surfactants, antioxidants, Examples include preservatives, preservatives, disinfectants, coating agents, colorants, fragrances, pH adjusters, and other anti-allergen ingredients. These components can be used alone or in combination of two or more.
溶剤としては、例えば、水；メタノール、エタノール、ｎ－プロパノール、イソプロパノール、ｎ－ブタノール、イソブタノール、第二ブタノール、第三ブタノール、ｎ－ヘキサノール等のアルコール類；エチレングリコール、ジエチレングリコール、トリエチレングリコール、テトラエチレングリコール、ポリオキシエチレングリコール２００、ポリオキシエチレングリコール４００、プロピレングリコール、ジプロピレングリコール、エチレングリコールモノメチルエーテル、エチレングリコールモノエチルエーテル、エチレングリコールモノブチルエーテル、エチレングリコールモノヘキシルエーテル、エチレングリコールモノ－２－エチルヘキシルエーテル、ジエチレングリコールモノエチルエーテル、ジエチレングリコールモノブチルエーテル、ジエチレングリコールモノヘキシルエーテル、ジエチレングリコールモノ－２－エチルヘキシルエーテル、トリエチレングリコールモノブチルエーテル、プロピレングリコールモノメチルエーテル、プロピレングリコールモノエチルエーテル、プロピレングリコールモノｎ－プロピルエーテル、プロピレングリコールモノｎ－ブチルエーテル、プロピレングリコールモノｎ－ブチルエーテル、ジプロピレングリコールモノメチルエーテル、ジプロピレングリコールモノエチルエーテル、トリプロピレングリコールモノメチルエーテル、３－メトキシブタノール、３－メチル－３－メトキシブタノール等のグリコールエーテル類等が挙げられる。中でも、水、又はアルコール類が好ましい。これらの溶剤は、１種単独で又は２種以上を組み合わせて用いることができる。 Examples of the solvent include water; alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tertiary-butanol, and n-hexanol; ethylene glycol, diethylene glycol, triethylene glycol, Tetraethylene glycol, polyoxyethylene glycol 200, polyoxyethylene glycol 400, propylene glycol, dipropylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monohexyl ether, ethylene glycol mono-2 - Ethylhexyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monohexyl ether, diethylene glycol mono-2-ethylhexyl ether, triethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol mono-n-propyl ether , propylene glycol mono-n-butyl ether, propylene glycol mono-n-butyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, tripropylene glycol monomethyl ether, 3-methoxybutanol, 3-methyl-3-methoxybutanol, and other glycols. Examples include ethers. Among these, water or alcohols are preferred. These solvents can be used alone or in combination of two or more.
本開示の組成物は、ヨウ化ポリビニルピロリドンと、必要に応じて他の成分とを組み合わせて常法により調製することができる。 The composition of the present disclosure can be prepared by a conventional method by combining polyvinylpyrrolidone iodide and other components as necessary.
本発明の組成物の形状は、特に限定されない。例えば、液体状（例えば、溶液状、懸濁液状等）、ペースト状、ゲル状、クリーム状又は固体状（例えば、粉末状、顆粒状等）等であってもよい。中でも、液体状であることが好ましい。 The shape of the composition of the present invention is not particularly limited. For example, it may be in a liquid form (for example, a solution, a suspension, etc.), a paste, a gel, a cream, or a solid (for example, a powder, a granule, etc.). Among these, a liquid state is preferable.
近年、卵アレルゲンは、環境中に存在していることが報告されている。そのため、本発明の組成物は、例えば、卵アレルゲンが存在し得る対象物に、噴霧、塗布、浸漬等により付着させて使用することができる。
卵アレルゲンが存在し得る対象物としては、特に限定されないが、例えば、衣料品、カーペット、ソファー、壁紙、カーテン等のインテリア類、布団側地、布団カバー、布団中綿、シーツ、枕カバー、マット等の寝具類、カーシート、カーマット、天井材及び床材等の自動車部品類、ぬいぐるみ、掃除用ウェットワイパー、マスク、フィルター材料、電気掃除機の集塵袋等の繊維や繊維製品等が挙げられる。
また、本開示の組成物は、洗濯時に使用する洗剤や柔軟仕上げ剤等に添加することもできる。
In recent years, egg allergens have been reported to exist in the environment. Therefore, the composition of the present invention can be used, for example, by adhering it to an object where an egg allergen may be present, by spraying, coating, dipping, or the like.
Objects in which egg allergens may exist are not particularly limited, but include, for example, clothing, carpets, sofas, wallpaper, interior items such as curtains, futon sides, futon covers, futon filling, sheets, pillowcases, mats, etc. These include bedding, car seats, car mats, automobile parts such as ceiling materials and flooring materials, fibers and textile products such as stuffed animals, wet wipes for cleaning, masks, filter materials, and dust collection bags for vacuum cleaners.
Furthermore, the composition of the present disclosure can also be added to detergents, fabric softeners, and the like used during washing.
なお、本開示の組成物による卵アレルゲン（より具体的には、環境中の卵アレルゲン）の活性低減効果は、後述する実施例に記載の評価方法（より具体的には、卵アレルゲンと、アレルギー患者血液より回収された卵アレルゲンに反応する血清中の抗卵アレルゲンＩｇＥ抗体とを反応させる方法）により、初めて確認されたものである。 The effect of the composition of the present disclosure on reducing the activity of egg allergens (more specifically, egg allergens in the environment) was determined by the evaluation method described in the Examples below (more specifically, the effect of reducing the activity of egg allergens and egg allergens in the environment) This was first confirmed by a method in which anti-egg allergen IgE antibodies in serum react with egg allergen collected from patient blood.
なお、本明細書において「含む」とは、「本質的にからなる」と、「からなる」をも包含する（The term "comprising" includes "consisting essentially of” and "consisting of."）。また、本開示は、本明細書に説明した構成要件の任意の組み合わせを全て包含する。 Note that in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." Additionally, the present disclosure encompasses any and all combinations of the features described herein.
また、上述した本開示の各実施形態について説明した各種特性（性質、構造、機能等）は、本開示に包含される主題を特定するにあたり、どのように組み合わせられてもよい。すなわち、本開示には、本明細書に記載される組み合わせ可能な各特性のあらゆる組み合わせからなる主題が全て包含される。 Further, the various characteristics (properties, structures, functions, etc.) described for each embodiment of the present disclosure described above may be combined in any manner in order to specify the subject matter covered by the present disclosure. That is, the present disclosure encompasses all subject matter consisting of any and all combinations of the combinable features described herein.
本開示の内容を以下の実施例を用いて具体的に説明する。しかし、本開示はこれらに何ら限定されるものではない。下記において、特に言及する場合を除いて、実験は大気圧及び常温条件下で行っている。また特に言及する場合を除いて、「％」は「質量％」を意味する。また、各表に記載される各成分の配合量値も特に断らない限り「質量％」を示す。 The content of the present disclosure will be specifically explained using the following examples. However, the present disclosure is not limited thereto. In the following, unless otherwise specified, experiments are conducted under atmospheric pressure and room temperature conditions. Further, unless otherwise specified, "%" means "% by mass". In addition, the blending amount of each component listed in each table is expressed in "% by mass" unless otherwise specified.
競合ＥＬＩＳＡ法により、卵アレルゲン不活化（活性低減）率を測定した。卵アレルゲン（ＯＶＡ）を１μｇ／ｍＬになるように調製し、ＥＬＩＳＡプレートに添加し、一晩４℃で静置し固相化した（ＯＶＡ固相プレート）。ＯＶＡと薬剤を９：１でアレルゲン濃度１０μｇ／ｍＬに調製し、一晩４℃で反応した（アレルゲン反応液）。薬剤の代わりに精製水を用いたものをコントロールとした。得られたアレルゲン反応液と、アレルギー患者血液より回収されたＯＶＡに反応する血清中の抗ＯＶＡ ＩｇＥ抗体とをＯＶＡ固相プレートに添加し、競合反応を行った。プレート上に固相化されたＯＶＡと結合した血清中の抗ＯＶＡ ＩｇＥ抗体と、酵素標識抗ＩｇＥ抗体とを結合させ、基質の発光を検出した。
血清中の抗ＯＶＡ ＩｇＥ抗体は、不活化されたＯＶＡとは結合しないことから、プレート上に固相化されたＯＶＡと結合する血清中の抗体が多い（発光強度が強い）ほど、不活化効果が高いと判断した。
Egg allergen inactivation (activity reduction) rate was measured by competitive ELISA method. Egg allergen (OVA) was prepared at 1 μg/mL, added to the ELISA plate, and left to stand at 4° C. overnight to solidify (OVA solid phase plate). OVA and drug were mixed at a ratio of 9:1 to an allergen concentration of 10 μg/mL, and reacted overnight at 4° C. (allergen reaction solution). The control used purified water instead of the drug. The obtained allergen reaction solution and an anti-OVA IgE antibody in the serum that reacts with OVA collected from the blood of an allergic patient were added to an OVA solid-phase plate to perform a competitive reaction. The anti-OVA IgE antibody in the serum bound to OVA immobilized on the plate was bound to the enzyme-labeled anti-IgE antibody, and the luminescence of the substrate was detected.
Since anti-OVA IgE antibodies in serum do not bind to inactivated OVA, the more antibodies in serum that bind to OVA immobilized on the plate (the stronger the luminescence intensity), the greater the inactivation effect. was judged to be high.
なお、薬剤としては、ヨウ化ポリビニルピロリドン（ＰＶＰ－Ｉ）０．０２％水溶液、ＰＶＰ－Ｉ ０．１％水溶液、０．１％ＰＶＰ－Ｉ ５５％アルコール溶液（ＰＶＰ－Ｉ ０．１％ ａｌｃ．５５％）、５５％エタノール溶液（５５％ＥｔＯＨ）、及びタンニン酸 ０．０１％水溶液を用いた。なお、タンニン酸の配合量が多くなると薬剤の褐変が生じることから、タンニン酸の濃度としては褐変の生じない０．０１％を選択した。 The drugs used include polyvinylpyrrolidone iodide (PVP-I) 0.02% aqueous solution, PVP-I 0.1% aqueous solution, 0.1% PVP-I 55% alcohol solution (PVP-I 0.1% alc). .55%), a 55% ethanol solution (55% EtOH), and a 0.01% tannic acid aqueous solution were used. In addition, since browning of the drug occurs when the amount of tannic acid blended increases, the concentration of tannic acid was selected to be 0.01%, which does not cause browning.
コントロールの５０％の蛍光強度を示すＯＶＡの濃度を５０％ ｉｎｈｉｂｉｔｉｏｎ濃度（ＩＣ５０）とし、薬剤のＩＣ５０からＩｇＥ結合相対力価とアレルゲン不活化率を以下の式を用いて算出した。
Ｉｎｈｉｂｉｔｉｏｎ（％）＝（コントロール蛍光強度－薬剤蛍光強度）／（コントロール蛍光強度－ブランク蛍光強度）×１００
ＩｇＥ結合相対力価＝コントロールＩＣ５０／薬剤ＩＣ５０
不活化率（％）＝（１－ＩｇＥ結合相対力価）×１００
結果を表１に示す。
The concentration of OVA exhibiting 50% of the fluorescence intensity of the control was defined as the 50% inhibition concentration (IC 50 ), and the IgE binding relative titer and allergen inactivation rate were calculated from the IC 50 of the drug using the following formulas.
Inhibition (%) = (control fluorescence intensity - drug fluorescence intensity) / (control fluorescence intensity - blank fluorescence intensity) x 100
IgE binding relative titer=Control IC50 /Drug IC50
Inactivation rate (%) = (1-IgE binding relative titer) x 100
The results are shown in Table 1.
表１に示すように、ヨウ化ポリビニルピロリドンはＯＶＡに対し高い活性低減効果を有することが確認された。なお、卵白はアルコールにより変性（凝集）することが知られているが、５５％ＥｔＯＨでは変性による活性低減効果は確認されなかった。また、ダニやスギ花粉等に対するアレルゲン活性低減作用が知られているタンニン酸は、ＯＶＡに対しての活性低減効果をほとんど示さないことが確認された。
As shown in Table 1, it was confirmed that polyvinylpyrrolidone iodide has a high activity-reducing effect on OVA. Although egg white is known to be denatured (agglomerated) by alcohol, no activity reduction effect due to denaturation was observed with 55% EtOH. Furthermore, it was confirmed that tannic acid, which is known to have an activity-reducing effect on allergen activity against dust mites, cedar pollen, etc., hardly exhibits an activity-reducing effect on OVA.
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