JP6700015B2 - Antifungal composition - Google Patents
Antifungal composition Download PDFInfo
- Publication number
- JP6700015B2 JP6700015B2 JP2015190263A JP2015190263A JP6700015B2 JP 6700015 B2 JP6700015 B2 JP 6700015B2 JP 2015190263 A JP2015190263 A JP 2015190263A JP 2015190263 A JP2015190263 A JP 2015190263A JP 6700015 B2 JP6700015 B2 JP 6700015B2
- Authority
- JP
- Japan
- Prior art keywords
- silver
- halide
- nanoparticles
- silver halide
- ion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000012871 anti-fungal composition Substances 0.000 title claims description 40
- -1 silver halide Chemical class 0.000 claims description 111
- 229910052709 silver Inorganic materials 0.000 claims description 79
- 239000004332 silver Substances 0.000 claims description 79
- 239000002105 nanoparticle Substances 0.000 claims description 58
- 239000002245 particle Substances 0.000 claims description 26
- 150000007524 organic acids Chemical class 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 229920003169 water-soluble polymer Polymers 0.000 claims description 13
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 239000003963 antioxidant agent Substances 0.000 claims description 4
- 230000003078 antioxidant effect Effects 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000003906 humectant Substances 0.000 claims description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 51
- 239000000243 solution Substances 0.000 description 26
- 239000000203 mixture Substances 0.000 description 21
- 239000000126 substance Substances 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- JKFYKCYQEWQPTM-UHFFFAOYSA-N 2-azaniumyl-2-(4-fluorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-UHFFFAOYSA-N 0.000 description 16
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- 238000002156 mixing Methods 0.000 description 14
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- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 13
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 10
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- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 8
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- 239000002781 deodorant agent Substances 0.000 description 2
- YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 description 2
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Description
本発明は、ハロゲン化銀ナノ粒子を含む抗真菌組成物に関する。 The present invention relates to antifungal compositions containing silver halide nanoparticles.
近年、各分野において、衛生面を重視する意識が高まる傾向にあり、様々な抗菌製品が開発されているが、カビなどの真菌に対する製品の開発はあまり進んでいないのが実情である。その原因として、細菌が核を持たない原核生物であるのに対し、真菌は人間と同じ核を持つ真核生物であるため、細胞毒性の低い薬剤が非常に限られていること、キチン質からなる強固な細胞壁をもつため、薬剤が細胞内部まで到達しにくいこと、などが挙げられる。また、真菌には、拭き掃除などで比較的簡単に除去できる表在性真菌のほか、風呂場のゴムパッキンに生えるクロカビや、皮下組織に生息する白癬菌など、除去が難しい深い部分に生息する深部表在性真菌が知られており、後者については未だ開発が充分なされていない。 In recent years, in each field, there is a growing tendency to emphasize hygiene, and various antibacterial products have been developed, but the fact is that the development of products against fungi such as mold has not progressed so much. The reason is that bacteria are prokaryotic organisms that have no nucleus, whereas fungi are eukaryotic organisms that have the same nucleus as humans, so there are very few drugs with low cytotoxicity. Since it has a strong cell wall, it is difficult for the drug to reach the inside of the cell. In addition to superficial fungi that can be removed relatively easily by wiping, fungi can also be found in deep areas that are difficult to remove, such as black mold that grows in the rubber packing in the bathroom and ringworm that lives in the subcutaneous tissues. Superficial fungi are known, and the latter has not been fully developed.
そこで、これらの問題を解決する方法として、マグネシウム、カルシウム、ストロンチウム、アルミニウム、マンガン、ニッケル、銅、及び、亜鉛からなる群の中から選ばれた2種以上の金属の難溶性オルトリン酸複塩に0.5〜5.0重量%の銀を担持させた抗菌・抗カビ噴霧剤や(特許文献1)、無機多孔質に銀や銅を担持させた水虫治療薬などが提案されている(特許文献2)。 Therefore, as a method for solving these problems, a poorly soluble orthophosphoric acid double salt of two or more metals selected from the group consisting of magnesium, calcium, strontium, aluminum, manganese, nickel, copper, and zinc is used. An antibacterial/antifungal spray agent carrying 0.5 to 5.0% by weight of silver and (patent document 1), a remedy for athlete's foot with silver or copper supported on an inorganic porous material, and the like have been proposed (patented). Reference 2).
特許文献1、2においては、いずれも抗菌剤として公知である銀を用いているが、いずれも粒径が大きいため、噴霧剤として用いるにはノズルがつまる、などの問題があり、使用形態が限定されていた。
そこで本発明は、より多くの形態での使用が可能である抗真菌組成物を提供するものである。
In Patent Documents 1 and 2, silver, which is known as an antibacterial agent, is used, but both have a problem that the nozzle is clogged when used as a propellant due to the large particle size, and the usage form is It was limited.
Therefore, the present invention provides an antifungal composition that can be used in more forms.
より多くの形態での使用を可能とするためには、抗真菌剤として作用する成分をナノサイズとすることが考えられるが、このような大きさとすると、分散が不安定になる傾向がある。本発明者は、鋭意研究の結果、抗真菌成分としてナノサイズの微粒子を用いながらも、分散安定性に優れる組成を見出した。さらに、本発明者は、当該組成は抗真菌作用について持続性、即効性にも優れることも見出した。 In order to enable use in more forms, it is conceivable that the component acting as an antifungal agent has a nano size, but such a size tends to make the dispersion unstable. As a result of earnest research, the present inventor has found a composition having excellent dispersion stability even when nano-sized fine particles are used as an antifungal component. Furthermore, the present inventor has also found that the composition has excellent antifungal action, and has excellent durability and immediate effect.
すなわち第1の発明は、粒径が1nm以上100nm以下であるハロゲン化銀からなるナノ粒子と、前記ハロゲン化銀を構成するハロゲンと同元素のハロゲン化物イオンと、少なくとも1種の水溶性高分子と、カルボキシル基を有する有機酸および/またはその塩とを含み、前記ハロゲン化銀中の銀と前記ハロゲン化物イオンのモル比が1:1〜1:1000であることを特徴とする抗真菌組成物である。 That is, the first invention is to provide nanoparticles comprising silver halide having a particle size of 1 nm or more and 100 nm or less, a halide ion of the same element as halogen constituting the silver halide, and at least one water-soluble polymer. And an organic acid having a carboxyl group and/or a salt thereof, and the molar ratio of silver to halide ion in the silver halide is 1:1 to 1:1000. It is a thing.
また第2の発明は、上記第1の発明において、前記抗真菌組成物が、界面活性剤、保湿剤、溶媒、および抗酸化剤からなる群から選ばれる少なくとも1種をさらに含むことを特徴とする抗真菌組成物である。 A second invention is characterized in that, in the above-mentioned first invention, the antifungal composition further comprises at least one selected from the group consisting of a surfactant, a humectant, a solvent, and an antioxidant. It is an antifungal composition.
本発明によれば、より多くの形態での使用が可能である抗真菌組成物を提供することが出来る。 According to the present invention, it is possible to provide an antifungal composition that can be used in various forms.
以下、本発明の抗真菌組成物の1つの実施形態について詳述する。本実施形態の抗真菌組成物は、ハロゲン化銀からなるナノ粒子と、ハロゲン化物イオンと、水溶性高分子と、カルボキシル基を有する有機酸(以下、単に有機酸ともいう)および/またはその塩とを含む。 Hereinafter, one embodiment of the antifungal composition of the present invention will be described in detail. The antifungal composition of the present embodiment comprises nanoparticles of silver halide, a halide ion, a water-soluble polymer, an organic acid having a carboxyl group (hereinafter, also simply referred to as an organic acid) and/or a salt thereof. Including and
本実施形態の抗真菌組成物は、例えば、銀塩と、ハロゲン化物と、水溶性高分子と、有機酸および/またはその塩とを溶液中で混合することにより製造することができる。銀塩とハロゲン化物とを混合することで銀塩とハロゲン化物とが反応し、ハロゲン化銀が生成される。各成分の割合は特に限定されないが、生成されるハロゲン化銀中に含有される銀とハロゲン化物イオンとのモル比が1:1〜1:1000となるように銀塩とハロゲン化物の比率(銀塩を構成する銀イオンとハロゲン化物を構成するハロゲン化物イオンの比率)が設定されることが好ましい。
なお、製造方法は当該方法には限定されず、例えば既に得られているハロゲン化銀ナノ粒子を含む組成物にハロゲン化物イオン、水溶性高分子、有機酸および/またはその塩を添加するなどして調製されるようにしてもよい。
The antifungal composition of the present embodiment can be produced, for example, by mixing a silver salt, a halide, a water-soluble polymer, an organic acid and/or a salt thereof in a solution. By mixing the silver salt and the halide, the silver salt and the halide react with each other to produce silver halide. The ratio of each component is not particularly limited, but the ratio of silver salt and halide (so that the molar ratio of silver and halide ion contained in the produced silver halide is 1:1 to 1:1000 ( It is preferable to set the ratio of silver ions forming the silver salt and halide ions forming the halide.
The production method is not limited to the method, and for example, a halide ion, a water-soluble polymer, an organic acid and/or a salt thereof may be added to a composition containing silver halide nanoparticles that has already been obtained. It may be prepared as follows.
本実施形態の抗真菌組成物に含まれるハロゲン化銀の殺菌性については従来から知られており、様々な殺菌組成物として利用されている。本実施形態では、その中でも非常に粒子径の小さい1nm以上100nm以下のナノ粒子状のものが利用できる。また、少量でも効率よく抗真菌性を発揮するようにする観点から、ハロゲン化銀ナノ粒子の粒子径は小さいほど好ましい。また、真菌の堅い細胞壁に浸透しやすくなる観点からも、ハロゲン化銀ナノ粒子の粒子径は小さいほど好ましい。一方で、粒子径が1nm未満であるとハロゲン化銀の物質としての安定性が低下する。そのため、良好な抗真菌性と良好な安定性とを得るために、ハロゲン化銀ナノ粒子の粒子径は、10nm未満1nm以上のシングルナノサイズであることがより好ましい。なお、当該粒子径は、例えば銀塩とハロゲン化物とを反応させるときの銀イオンとハロゲン化物イオンとの割合を調整するなどして制御することができる。また、ハロゲン化銀は結晶性が低く、低温での合成では結晶性が低いアモルファスな結晶が合成され、高温での合成においては結晶性が良いナノ粒子を得ることができる。本実施形態においてはいずれの結晶も使用することができ、特に限定されない。 The bactericidal property of the silver halide contained in the antifungal composition of the present embodiment has been conventionally known and used as various bactericidal compositions. In the present embodiment, among them, nanoparticles having a very small particle diameter of 1 nm or more and 100 nm or less can be used. Further, from the viewpoint of efficiently exhibiting antifungal properties even in a small amount, it is preferable that the silver halide nanoparticles have a small particle size. Also, from the viewpoint of facilitating penetration into the rigid cell wall of fungi, it is preferable that the silver halide nanoparticles have a small particle diameter. On the other hand, if the grain size is less than 1 nm, the stability of the silver halide as a substance is reduced. Therefore, in order to obtain good antifungal properties and good stability, the particle size of the silver halide nanoparticles is more preferably a single nanosize of less than 10 nm and 1 nm or more. The particle size can be controlled, for example, by adjusting the ratio of silver ions and halide ions when reacting the silver salt and the halide. Further, silver halide has low crystallinity, and an amorphous crystal with low crystallinity is synthesized by synthesizing at low temperature, and nanoparticles having good crystallinity can be obtained by synthesizing at high temperature. In this embodiment, any crystal can be used, and there is no particular limitation.
上述のとおり、ハロゲン化銀ナノ粒子は、例えば銀塩とハロゲン化物とを反応させることにより得ることができる。
銀塩としては、硝酸銀、亜硝酸銀、塩素酸銀、過塩素酸銀、酢酸銀及び硫酸銀などが挙げられ、ハロゲン化物としては、塩化ナトリウム、塩化カリウム、ヨウ化カリウム、塩化リチウム、塩化銅(II)、塩化銀、フッ化塩素などが挙げられるが、これらの組合せについては、実際に使用したいハロゲン化銀に併せて自由に選択する事ができる。
As described above, the silver halide nanoparticles can be obtained, for example, by reacting a silver salt with a halide.
Examples of silver salts include silver nitrate, silver nitrite, silver chlorate, silver perchlorate, silver acetate and silver sulfate, and halides include sodium chloride, potassium chloride, potassium iodide, lithium chloride, copper chloride ( II), silver chloride, chlorine fluoride and the like can be mentioned, and the combination thereof can be freely selected according to the silver halide to be actually used.
本実施形態の抗真菌組成物に関する上述のとおり例示した調製において、銀塩とハロゲン化物の比率については、ハロゲン化物が銀塩に対し、化学量論的に過剰であることが望ましい。具体的には、本実施形態の抗真菌組成物中に存在するハロゲン化銀中の銀と、ハロゲン化物イオン(銀イオンと反応せずに組成物中にイオンとして存在しているハロゲン化物イオン)とのモル比が、1:1〜1:1000となるように、銀塩を構成する銀イオンと、ハロゲン化物を構成するハロゲン化物イオンのモル比を設定することが好ましい。特に、本実施形態においては、銀イオンとハロゲン化物イオンとの間のモル比の差が大きくなるほど粒子径の小さいハロゲン化銀ナノ粒子が得られるため好ましい。 In the preparation exemplified above as to the antifungal composition of the present embodiment, it is desirable that the halide is in a stoichiometric excess with respect to the silver salt with respect to the ratio of the silver salt and the halide. Specifically, the silver in the silver halide present in the antifungal composition of the present embodiment and the halide ion (the halide ion present as an ion in the composition without reacting with the silver ion) It is preferable to set the molar ratio of the silver ions forming the silver salt and the halide ions forming the halide so that the molar ratio thereof is 1:1 to 1:1000. Particularly, in the present embodiment, it is preferable that the difference in the molar ratio between the silver ion and the halide ion is larger because silver halide nanoparticles having a smaller particle size can be obtained.
1:1よりもハロゲン化物イオンの割合が小さくなると、組成物の調製において全てのハロゲン化物イオンが銀イオンと反応し、ハロゲン化銀ナノ粒子の周囲に後述の電気二重層が形成されなくなる。その結果、ハロゲン化銀ナノ粒子のゼータ電位が低下し、粒子が凝集して沈降するか、或いは粒子同士が結合して粒子径が大きくなって沈降するなどして、ハロゲン化銀ナノ粒子の分散安定性が低下する。一方、1:1000よりもハロゲン化物イオンの割合が多くなると、ハロゲン化物イオンが過剰になりすぎて、銀と錯体を形成してしまう。
なお、本明細書でいうハロゲン化物イオンとは、フッ化物イオン(F-)、塩化物イオン(Cl-)、臭化物イオン(Br-)、ヨウ化物イオン(I-)、アスタチン化物イオン(At-)などが挙げられる。
また、組成物の調製において銀塩の溶液とハロゲン化物の溶液を混合する工程を含む場合には、両液の接触時間が短いほど粒子径の小さいハロゲン化銀ナノ粒子が得られるため、当該工程をできるだけ短時間で行うことが好ましい。
When the ratio of halide ions is less than 1:1, all the halide ions react with silver ions in the preparation of the composition, and the electric double layer described below is not formed around the silver halide nanoparticles. As a result, the zeta potential of the silver halide nanoparticles decreases, the particles aggregate and settle, or the particles are bound to each other to increase in particle size and settle, resulting in dispersion of the silver halide nanoparticles. Stability decreases. On the other hand, when the ratio of halide ions is more than 1:1000, the halide ions become excessive and form a complex with silver.
In addition, the halide ion in the present specification means a fluoride ion (F-), a chloride ion (Cl-), a bromide ion (Br-), an iodide ion (I-), an astatine ion (At- ) And the like.
Further, when the step of mixing a solution of a silver salt and a solution of a halide is included in the preparation of the composition, the shorter the contact time between the two solutions is, the smaller the grain size of the silver halide nanoparticles is, so that the step is concerned. Is preferably performed in the shortest possible time.
ここで、本実施形態でハロゲン化銀ナノ粒子の周囲に形成される電気二重層について説明する。ハロゲン化物は溶液中ではハロゲン化物イオンとして存在しており、銀塩が水に溶解してできた銀イオンと反応してハロゲン化銀のナノ粒子を生成する。生成されたハロゲン化銀ナノ粒子は溶液中に存在する過剰のハロゲン化物イオンを吸着してマイナスの電荷を帯び、さらに吸着されたハロゲン化銀イオンは過剰のハロゲン化物イオンの対イオンを吸着する。これによりハロゲン化銀ナノ粒子の周囲には電気二重層が形成される。当該電気二重層がその周囲に形成されたハロゲン化銀ナノ粒子は、高いゼータ電位を有することで、分散安定化する。 Here, the electric double layer formed around the silver halide nanoparticles in the present embodiment will be described. The halide exists as a halide ion in the solution, and reacts with the silver ion formed by dissolving the silver salt in water to form silver halide nanoparticles. The produced silver halide nanoparticles adsorb excess halide ions present in the solution and are negatively charged, and the adsorbed silver halide ions adsorb counter ions of the excess halide ions. As a result, an electric double layer is formed around the silver halide nanoparticles. The silver halide nanoparticles around which the electric double layer is formed have high zeta potential, and thus are stabilized in dispersion.
本実施形態においては、この分散安定化したハロゲン化銀ナノ粒子を、分散剤である水溶性高分子が保護している。また、有機酸および/またはその塩がハロゲン化銀ナノ粒子の凝集を抑制する。これにより、ハロゲン化銀ナノ粒子の分散安定性を極めて高めることができるので、粒子サイズが数nmであっても、長期間、ハロゲン化銀ナノ粒子の凝集を抑制することができる。 In this embodiment, the dispersion-stabilized silver halide nanoparticles are protected by a water-soluble polymer as a dispersant. Further, the organic acid and/or its salt suppresses the aggregation of the silver halide nanoparticles. Thereby, the dispersion stability of the silver halide nanoparticles can be remarkably enhanced, so that the aggregation of the silver halide nanoparticles can be suppressed for a long period of time even if the particle size is several nm.
水溶性高分子は、ハロゲン化銀ナノ粒子の分散性を上げるものであれば特に制限はないが、一例として、ヒドロキシプロピルセルロース、ポリビニルピロリドンおよびポリビニルアルコールなどの水溶性高分子が挙げられる。これらの水溶性高分子は、様々な分子量のものがあり、いずれも使用することができるが、分子量が高くなるに従い、粒径の小さいハロゲン化銀ナノ粒子が得られるため、500以上の分子量の水溶性高分子が好適に用いられる。 The water-soluble polymer is not particularly limited as long as it enhances the dispersibility of silver halide nanoparticles, and examples thereof include water-soluble polymers such as hydroxypropyl cellulose, polyvinylpyrrolidone and polyvinyl alcohol. These water-soluble polymers have various molecular weights, and any of them can be used. However, as the molecular weight becomes higher, silver halide nanoparticles having a smaller particle size can be obtained. Water-soluble polymers are preferably used.
カルボキシル基(-COOH)を有する有機酸および/またはその塩としては、特に制限はないが、クエン酸、乳酸、リンゴ酸、酒石酸、コハク酸、アスコルビン酸、グリコール酸や、これらの塩などのオキシカルボン酸が好適に挙げられ、中でもクエン酸がより好適に用いられる。 The organic acid having a carboxyl group (-COOH) and/or its salt is not particularly limited, but citric acid, lactic acid, malic acid, tartaric acid, succinic acid, ascorbic acid, glycolic acid, and oxy-acids of these salts and the like. Carboxylic acid is preferably used, and citric acid is more preferably used.
本実施形態で分散安定なハロゲン化銀ナノ粒子を含む分散液を調製する場合、ハロゲン化銀ナノ粒子の凝集を防止することが重要となる。ハロゲン化銀ナノ粒子の凝集は粒子が有するゼータ電位に大きく影響されるため、有機酸および/またはその塩を用い、分散液のpHを酸性側にし、ハロゲン化銀ナノ粒子のゼータ電位を高くすることで、凝集を抑制できる。本実施形態において、水溶性高分子および有機酸および/またはその塩の割合は特に限定されず、適宜設定できるが、有機酸および/またはその塩の添加量は、水溶液のpHを2.0〜6.0に調整する量であることが好ましい。また、ハロゲン化銀ナノ粒子の粒子径を制御するためには、ハロゲン化銀ナノ粒子の主成分である銀イオンの溶液中からの供給を、如何に制御するかが重要となる。つまり、ハロゲン化銀ナノ粒子の合成時に反応に寄与せず組成物中に残っている銀イオンや、経時変化により、ナノ粒子から溶出してきた銀イオンなどによるナノ粒子の粒子成長を如何に阻害するかが重要となる。有機酸および/またはその塩は銀イオンと錯体を形成し安定化しやすいため、上述の銀イオンが粒子成長に関与するのを阻害できる。このうち、オキシカルボン酸、特にクエン酸は、銀イオンと錯体を形成し安定化しやすい。従って、pH調整剤としてオキシカルボン酸(より好ましくはクエン酸)を用いることが、数nmの極めて小さい粒子径で、且つ、分散安定性に優れたハロゲン化銀ナノ粒子を合成する上で、より好適である。 When preparing a dispersion liquid containing dispersion-stable silver halide nanoparticles in this embodiment, it is important to prevent aggregation of the silver halide nanoparticles. Aggregation of silver halide nanoparticles is greatly affected by the zeta potential of the particles. Therefore, use organic acid and/or its salt to adjust the pH of the dispersion to the acidic side to increase the zeta potential of silver halide nanoparticles. Therefore, aggregation can be suppressed. In the present embodiment, the ratio of the water-soluble polymer and the organic acid and/or its salt is not particularly limited and can be set as appropriate, but the amount of the organic acid and/or its salt added is such that the pH of the aqueous solution is 2.0 to The amount is preferably adjusted to 6.0. In order to control the particle size of the silver halide nanoparticles, it is important to control the supply of silver ions, which is the main component of the silver halide nanoparticles, from the solution. In other words, how to inhibit the particle growth of nanoparticles due to silver ions remaining in the composition that do not contribute to the reaction during the synthesis of silver halide nanoparticles and silver ions that have been eluted from the nanoparticles due to aging. Is important. Since the organic acid and/or its salt easily forms a complex with silver ions and is stabilized, it is possible to prevent the above-mentioned silver ions from participating in grain growth. Of these, oxycarboxylic acids, especially citric acid, tend to form a complex with silver ions and stabilize. Therefore, using an oxycarboxylic acid (more preferably citric acid) as a pH adjuster is more preferable in synthesizing silver halide nanoparticles having an extremely small particle size of several nm and excellent dispersion stability. It is suitable.
上記の各成分を混合するなどして得られた本実施形態の抗真菌組成物は、その形態については特に限定されず、例えば溶液状以外にも、ゾル、ゲルなど、組成物が流動性を有する態様とすることができる。 The antifungal composition of the present embodiment obtained by, for example, mixing the above components is not particularly limited in its form, and for example, in addition to solution form, sol, gel, etc., the composition exhibits fluidity. It is possible to have an aspect having.
本実施形態の抗真菌組成物は、界面活性剤、溶媒、および抗酸化剤からなる群から選ばれる少なくとも1種をさらに含んでいてもよい。これらの成分は、通常、銀塩、ハロゲン化物、水溶性高分子、有機酸および/またはその塩とを溶液中で混合してハロゲン化銀ナノ粒子を生成させた後に組成物中に添加することができるほか、これに限定されず、例えばハロゲン化銀ナノ粒子を生成する前に添加してもよい。 The antifungal composition of the present embodiment may further contain at least one selected from the group consisting of a surfactant, a solvent, and an antioxidant. These components are usually added to the composition after mixing with a silver salt, a halide, a water-soluble polymer, an organic acid and/or a salt thereof in a solution to form silver halide nanoparticles. In addition to the above, the present invention is not limited to this, and may be added before, for example, silver halide nanoparticles are formed.
界面活性剤としては、イオン性界面活性剤、非イオン性界面活性剤など適宜利用できるが、刺激性の観点から非イオン性の界面活性剤が好ましい。非イオン性界面活性剤の例としては、ポリオキシアルキルエーテル、グリセリン脂肪酸エステル、有機酸モノグリセリド、ポリグリセリン脂肪酸エステル、プロピレングリコール脂肪酸エステル、ポリグリセリン縮合リシノレイン酸エステル、ソルビタン脂肪酸エステル、ショ糖脂肪酸エステル、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステルなどが挙げられる。界面活性剤を配合すると、微細なミセルの状態で本実施形態の抗真菌組成物が、皮膚表面にまんべんなく行き渡りやすくなり、さらに有効成分であるハロゲン化銀のナノ粒子が、表皮細胞に浸透しやすくなるため、白癬菌のように、角質や皮下組織に生息する深部表在性真菌と接触しやすくなる。 As the surfactant, an ionic surfactant, a nonionic surfactant, and the like can be appropriately used, but a nonionic surfactant is preferable from the viewpoint of irritation. Examples of the nonionic surfactant, polyoxyalkyl ether, glycerin fatty acid ester, organic acid monoglyceride, polyglycerin fatty acid ester, propylene glycol fatty acid ester, polyglycerin condensed ricinoleic acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, Examples thereof include polyoxyethylene fatty acid ester and polyoxyethylene sorbitan fatty acid ester. When a surfactant is blended, the antifungal composition of the present embodiment in the form of fine micelles is evenly distributed on the skin surface, and further, nanoparticles of silver halide as an active ingredient are easily penetrated into epidermal cells. Therefore, it becomes easy to contact deep surface superficial fungi such as Trichophyton which inhabit the keratin and subcutaneous tissues.
また本実施形態の抗真菌組成物を水虫治療剤などに用いる場合、保湿剤などを添加してもよい。保湿剤としては、セラミド類、フィトスフィンゴシンなどの各種角質細胞間脂質;ヒアルロン酸ナトリウムなどのヒアルロン酸塩とその酸誘導体;ポリプロピレングリコール、ポリエチレングリコール、エチルへキサンジオール、ヘキシレングリコール、グリセリン、プロピレングリコール、ソルビトール、ヘキサンジオール、カプリルグリコールなどの各種のポリオールが挙げられる。これらのうちでセラミド類やフィトスフィンゴシンは、優れた皮膚に対する潤いを保つ作用を有しており、皮膚のキメを整えるので好ましい。中でも、セラミド類は、損傷を受けた皮膚に特に必要とされる物質であるため好ましい。 When the antifungal composition of the present embodiment is used as a remedy for athlete's foot etc., a moisturizer etc. may be added. As humectants, various keratinic intercellular lipids such as phytosphingosine; hyaluronates such as sodium hyaluronate and its acid derivatives; polypropylene glycol, polyethylene glycol, ethylhexanediol, hexylene glycol, glycerin, propylene glycol , Various kinds of polyols such as sorbitol, hexanediol, and capryl glycol. Among these, ceramides and phytosphingosine are preferable because they have an excellent effect of keeping the skin moist and maintain the texture of the skin. Among them, ceramides are preferable because they are substances particularly required for damaged skin.
溶媒としては、水のほか、濡れ性等の向上のために、エタノール及びイソプロパノールのようなアルコール; ジエチレングリコールモノメチルエーテル、ジエチレングリコールブチルエーテル、ジエチレングリコールモノエチルエーテル、及びジエチレングリコールジブチルエーテルのようなグリコールエーテル; ポリエチレングリコール−300及びポリエチレングリコール−400のようなポリエチレングリコール; プロピレングリコール及びグリセリンのようなグリコール; 2−ピロリドン及びN−メチル− 2−ピロリドンのようなピロリドン; グリセロールホルマル; ジメチルスルホキシド; ジブチルセベケート; ポリソルベート80のようなポリオキシエチレンソルビタンエステル; 及びこれらの混合物などの有機溶媒を添加してもよい。 As the solvent, in addition to water, alcohols such as ethanol and isopropanol for improving wettability; glycol ethers such as diethylene glycol monomethyl ether, diethylene glycol butyl ether, diethylene glycol monoethyl ether, and diethylene glycol dibutyl ether; polyethylene glycol- Polyethylene glycols such as 300 and polyethylene glycol-400; glycols such as propylene glycol and glycerin; pyrrolidones such as 2-pyrrolidone and N-methyl-2-pyrrolidone; glycerol formal; dimethyl sulfoxide; dibutyl sebecate; polysorbate 80 Organic solvents such as polyoxyethylene sorbitan ester; and mixtures thereof may be added.
さらに本実施形態の抗真菌組成物の劣化を防止するために、抗酸化剤が好適に用いられてもよい。具体的には、亜硫酸水素ナトリウム、亜硫酸ナトリウム、メタ亜硫酸水素ナトリウム、チオ硫酸ナトリウム、ホルムアルデヒドスルホキシル酸ナトリウム、l − アスコルビン酸、エリトルビン酸、アセチルシステイン、システイン、モノチオグリセロール、チオグリコール酸、チオ乳酸、チオ尿素、ジチオスレイトール、ジチオエリスレイトール、グルタチオン、パルミチン酸アスコルビル、ブチル化ヒドロキシアニソール、ブチル化ヒドロキシトルエン、ノルジヒドログアヤレチック酸、没食子酸プロピル、α − トコフェロール、及びこれらの混合物などから適宜選択できる。 Further, in order to prevent the deterioration of the antifungal composition of this embodiment, an antioxidant may be preferably used. Specifically, sodium bisulfite, sodium sulfite, sodium metabisulfite, sodium thiosulfate, sodium formaldehyde sulfoxylate, l-ascorbic acid, erythorbic acid, acetylcysteine, cysteine, monothioglycerol, thioglycolic acid, thiolactic acid. , Thiourea, dithiothreitol, dithioerythreitol, glutathione, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, nordihydroguaiaretic acid, propyl gallate, α-tocopherol, and mixtures thereof. It can be selected appropriately.
このようにして得られた抗真菌組成物は、様々な形態、方法で使用することができる。 The antifungal composition thus obtained can be used in various forms and methods.
例えば、上述のように、風呂場などのクロカビに使用する場合は、スプレーなどに入れて直接カビに噴霧する他、まだクロカビが生えていない場所に事前に噴霧しておくことで、防カビ効果が発揮できる。本実施形態の抗真菌組成物は、ハロゲン化銀のナノ粒子を含んで構成されているため、噴霧されたハロゲン化銀がその場に留まり、長期間、効果を持続するからである。 For example, as mentioned above, when using it for black mold in a bathroom, etc., put it in a spray etc. and spray it directly on the mold, or spray it in a place where black mold has not yet grown, to prevent the mold. Can be demonstrated. This is because the antifungal composition of the present embodiment is configured to include silver halide nanoparticles, and thus the sprayed silver halide remains in place and the effect is maintained for a long time.
また別の例として、水虫などの外用薬として用いる場合、スプレーなどに入れて患部に直接分蒸する他、ガーゼや不織布等に含浸させて貼付してもよいし、ワセリン、パラフィン、シリコン、プラスチベース、植物油、ミツロウ、ラノリンなど、公知の基剤と混ぜて軟膏として用いてもよい。さらに、本実施形態に係るハロゲン化銀ナノ粒子は、抗真菌性の他、殺菌性も有しているため、ブーツや革靴など、通気性が悪いような靴に噴霧したり、靴の中敷に含浸させて使用することで、水虫予防になる他、細菌が汗などを分解することで発生する臭いについても防止する事ができる。この時、マスキング剤などの消臭剤と併用することで、消臭性を向上させることができる。 As another example, when used as an external medicine for athlete's foot etc., it may be put in a spray etc. and directly steamed on the affected area, or it may be attached by impregnating it with gauze or a non-woven fabric, petrolatum, paraffin, silicone, plastic base. , Ointment may be mixed with a known base such as vegetable oil, beeswax, and lanolin. Furthermore, since the silver halide nanoparticles according to the present embodiment have antibacterial properties as well as bactericidal properties, they can be sprayed onto shoes with poor air permeability, such as boots and leather shoes, and insoles. By impregnating and using it, not only can athlete's foot be prevented, but also the odor generated when bacteria decompose sweat or the like can be prevented. At this time, the deodorant property can be improved by using it together with a deodorant such as a masking agent.
本実施形態の抗真菌組成物が効果を示す真菌としては、例えば、Trichophyton rubrum・Trichophyton mentagrophytes・Trichophyton tonsurans・Microsporum canis・Microsporum gypseum・Trichophyton verrucosum などの白癬菌や、 Aspergillus niger ・ Aspergillus ochraceus ・Aspergillus oryzaeなどのコウジカビ、食品などに生えるEupenicillium属、Hailer属、Penicilliopsis属、Talaromyces属、Trichocoma属に属するアオカビ、JISの抗カビ試験で指定されているEurotium tonophilum、Penicillium citrinum、Penicillium pinophilum、Rhizopus oryzae、Cladosporium cladosporioides、Aureobasidium pullulans、Trichoderma virens、Chaetomium globosum、Myrothecium verrucariaなどが挙げられるが、これに限るものではない。 Examples of fungi in which the antifungal composition of the present embodiment exhibits effects include, for example, Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, Microsporum gypseum, Trichophyton verrucosum, and other tinea fungi, Aspergillus niger, Aspergillus ochraceus, and Aspergillus ochraceus Of Aspergillus niger, Eugenicillium, Hailer, Penicilliopsis, Talaromyces, Trichocoma that grows in foods, etc., Eurotium tonophilum, Penicillium citrinum, Penicillium pinophilum, Rhizopus oryzae Examples include Aureobasidium pullulans, Trichoderma virens, Chaetomium globosum, Myrothecium verrucaria, but are not limited thereto.
以上、本実施形態によれば、より多くの形態での使用が可能である抗真菌組成物を提供することが出来る。例えば、有効成分の一つとしてハロゲン化銀という無機化合物のナノ粒子を用いるため、噴霧剤などの使用形態としたときにノズル詰まりなどの問題が生じがたい。また、使用時に広範囲に噴霧することができ、噴霧後もその場に長く留まり効果を持続することができる。
また、本実施形態の抗真菌組成物においては、上述のハロゲン化銀を構成しているハロゲン元素と同一種類のハロゲン化物イオンを含有している。当該ハロゲン化物イオンはハロゲン化銀ナノ粒子に吸着されており、当該ハロゲン化物イオンの吸着によりハロゲン化銀ナノ粒子の周囲に電気二重層が形成されており、その電気二重層が周囲に形成されたハロゲン化銀ナノ粒子を水溶性高分子で保護する。さらに本実施形態の抗真菌組成物に含有される有機酸および/またはその塩がハロゲン化銀ナノ粒子の凝集を抑制する。よって、本実施形態によれば、含有されるハロゲン化銀ナノ粒子の分散性に優れた抗真菌組成物が得られる。ナノ粒子の状態でハロゲン化銀粒子が分散していることで、少量でも効果的に抗真菌効果が得られる。
また、本実施形態の抗真菌組成物において、有機酸および/または塩としてクエン酸などのオキシカルボン酸を含有することで、ハロゲン化銀ナノ粒子が再凝集するのをより抑制することができるため、より長期間、性能を維持することができる。
As described above, according to this embodiment, it is possible to provide an antifungal composition that can be used in more forms. For example, since nanoparticles of an inorganic compound called silver halide are used as one of the active ingredients, problems such as nozzle clogging are less likely to occur when a spray agent or the like is used. In addition, it can be sprayed over a wide range at the time of use, and can remain in place for a long time even after spraying to maintain the effect.
Further, the antifungal composition of the present embodiment contains a halide ion of the same type as the halogen element constituting the above silver halide. The halide ion is adsorbed on the silver halide nanoparticle, and an electric double layer is formed around the silver halide nanoparticle by the adsorption of the halide ion, and the electric double layer is formed on the periphery. Protect silver halide nanoparticles with a water-soluble polymer. Furthermore, the organic acid and/or salt thereof contained in the antifungal composition of the present embodiment suppresses aggregation of silver halide nanoparticles. Therefore, according to this embodiment, an antifungal composition having excellent dispersibility of the contained silver halide nanoparticles can be obtained. Since the silver halide grains are dispersed in the form of nanoparticles, an antifungal effect can be effectively obtained even in a small amount.
Further, in the antifungal composition of the present embodiment, by containing an oxycarboxylic acid such as citric acid as the organic acid and/or salt, it is possible to further suppress reaggregation of the silver halide nanoparticles. The performance can be maintained for a longer period of time.
次に、実施例を挙げて本発明をより具体的に説明する。ただし、本発明はこれらの実施例のみに限定されるものではない。 Next, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.
(実施例1)
0.8Mのヨウ化カリウム溶液320 mL(純度KI 99%(和光純薬製))に対し、ポリビニルピロリドン(Across organics製、分子量3500)を1 vol%、さらに、クエン酸(純度98%(和光純薬製))を0.02 %添加し、完全溶解するまで攪拌した。別の容器に、0.5Mの硝酸銀溶液50 mL(純度99.8%(和光純薬製))を、遮蔽容器内で作製した。銀イオン:ヨウ化物イオンのモル比率が1:10になるように設定して上記2つの溶液を瞬時に攪拌混合し、実施例1の抗真菌組成物を得た。ここで、得られた抗真菌組成物に含まれるヨウ化銀ナノ粒子の粒子径をゼータ電位・粒経測定システム(大塚電子製、レーザードップラー法(動的・電気泳動光散乱法))により測定したところ、この時の平均粒子径は4.2nmであった。なお、ここでいう平均粒子径とは、体積平均粒子径のことをいう。
さらに、このヨウ化銀ナノ粒子組成物を透過型電子顕微鏡(日本電子社製JEM-2100)にて観察した。その写真を図1に示す。
(Example 1)
To 320 mL of 0.8 M potassium iodide solution (purity KI 99% (Wako Pure Chemical Industries)), 1% by volume of polyvinylpyrrolidone (Across organics, molecular weight 3500) and citric acid (purity 98% (Wako Pure Chemical Industries, Ltd.) 0.02% was added and stirred until completely dissolved. In another container, 50 mL of 0.5 M silver nitrate solution (purity 99.8% (manufactured by Wako Pure Chemical Industries)) was prepared in a shielded container. The antifungal composition of Example 1 was obtained by setting the molar ratio of silver ion: iodide ion to be 1:10 and stirring and mixing the above two solutions instantaneously. Here, the particle size of the silver iodide nanoparticles contained in the obtained antifungal composition is measured by a zeta potential/particle diameter measurement system (Otsuka Electronics, laser Doppler method (dynamic/electrophoretic light scattering method)) As a result, the average particle diameter at this time was 4.2 nm. The average particle size referred to here is the volume average particle size.
Further, the silver iodide nanoparticle composition was observed with a transmission electron microscope (JEM-2100 manufactured by JEOL Ltd.). The photograph is shown in FIG.
(実施例2)
実施例1で得られた抗真菌組成物を1.0wt%、ヨウ化カリウム(純度KI 99%(和光純薬製))0.5wt%、クエン酸1水和物(純度98%(和光純薬製))1.0wt%、ポリビニルピロリドン(Across organics製、分子量3500)0.1wt%、残りは純水として混合し、実施例1と比較してヨウ化物イオンに対するヨウ化銀の割合が低い抗真菌組成物を実施例2として作成した。この組成物の銀イオン:ヨウ化物イオンのモル比率(実施例1の溶液混合時における銀イオン:実施例1の溶液混合時におけるヨウ化物イオンおよび実施例2で新たに添加されたヨウ化カリウム由来のヨウ化物イオンの和)は1:56であった。含有されるヨウ化銀ナノ粒子の平均粒子径は3.8nmであった。
(Example 2)
1.0 wt% of the antifungal composition obtained in Example 1, 0.5 wt% of potassium iodide (purity KI 99% (manufactured by Wako Pure Chemical Industries)), citric acid monohydrate (purity 98% (manufactured by Wako Pure Chemical Industries, Ltd. )) 1.0 wt%, polyvinylpyrrolidone (Across organics, molecular weight 3500) 0.1 wt%, the rest is mixed as pure water, and the antifungal composition has a lower ratio of silver iodide to iodide ion as compared to Example 1. Was prepared as Example 2. The molar ratio of silver ion:iodide ion of this composition (derived from silver ion during solution mixing of Example 1: iodide ion during solution mixing of Example 1 and potassium iodide newly added in Example 2) The sum of iodide ions) was 1:56. The average particle size of the contained silver iodide nanoparticles was 3.8 nm.
(実施例3)
実施例1で得られた抗真菌組成物を1.0wt%、ヨウ化カリウム(純度KI 99%(和光純薬製))1wt%、クエン酸1水和物(純度98%(和光純薬製))0.1wt%、ポリビニルピロリドン(Across organics製、分子量3500)0.1wt%、残りは純水として混合し、実施例1と比較してヨウ化物イオンに対するヨウ化銀の割合が低い抗真菌組成物を実施例3として作成した。この組成物の銀イオン:ヨウ化物イオンのモル比率(実施例1の溶液混合時における銀イオン:実施例1の溶液混合時におけるヨウ化物イオンおよび実施例3で新たに添加されたヨウ化カリウム由来のヨウ化物イオンの和)は1:100であった。含有されるヨウ化銀ナノ粒子の平均粒子径は2.5nmであった。
(Example 3)
1.0 wt% of the antifungal composition obtained in Example 1, potassium iodide (purity KI 99% (manufactured by Wako Pure Chemical Industries)) 1 wt%, citric acid monohydrate (purity 98% (manufactured by Wako Pure Chemical Industries, Ltd.) ) 0.1 wt%, polyvinylpyrrolidone (manufactured by Across organics, molecular weight 3500) 0.1 wt%, and the rest was mixed as pure water to prepare an antifungal composition having a lower ratio of silver iodide to iodide ion as compared with Example 1. It was created as Example 3. Molar ratio of silver ion:iodide ion of this composition (derived from silver ion during solution mixing of Example 1: iodide ion during solution mixing of Example 1 and potassium iodide newly added in Example 3) The sum of iodide ions) was 1:100. The average particle size of the contained silver iodide nanoparticles was 2.5 nm.
(実施例4)
実施例1で得られた抗真菌組成物を0.33wt%、ヨウ化カリウム(純度KI 99%(和光純薬製))3wt%、クエン酸1水和物(純度98%(和光純薬製))0.5wt%、ポリビニルピロリドン(Across organics製、分子量3500)0.1wt%、残りは純水として混合し、実施例1と比較してヨウ化物イオンに対するヨウ化銀の割合が低い抗真菌組成物を実施例4として作成した。この組成物の銀イオン:ヨウ化物イオンのモル比率(実施例1の溶液混合時における銀イオン:実施例1の溶液混合時におけるヨウ化物イオンおよび実施例4で新たに添加されたヨウ化カリウム由来のヨウ化物イオンの和)は1:812であった。含有されるヨウ化銀ナノ粒子の平均粒子径は1.3nmであった。
(Example 4)
0.33 wt% of the antifungal composition obtained in Example 1, 3 wt% of potassium iodide (purity KI 99% (manufactured by Wako Pure Chemical Industries)), citric acid monohydrate (purity 98% (manufactured by Wako Pure Chemical Industries, Ltd.) ) 0.5 wt%, polyvinylpyrrolidone (manufactured by Across organics, molecular weight 3500) 0.1 wt%, and the rest was mixed as pure water to prepare an antifungal composition having a lower ratio of silver iodide to iodide ion as compared with Example 1. It was created as Example 4. Molar ratio of silver ion: iodide ion of this composition (derived from silver ion during solution mixing of Example 1: iodide ion during solution mixing of Example 1 and potassium iodide newly added in Example 4) Sum of iodide ions) was 1:812. The average particle size of the contained silver iodide nanoparticles was 1.3 nm.
(比較例1)
ヨウ化カリウム(純度KI 99%(和光純薬製))3wt%、クエン酸1水和物(純度98%(和光純薬製))0.1wt%、ポリビニルピロリドン(Across organics製、分子量3500)0.1wt%、残りは純水とし、ヨウ化銀を含まない溶液を作成した。
(Comparative Example 1)
Potassium iodide (purity KI 99% (Wako Pure Chemical Industries)) 3 wt%, citric acid monohydrate (purity 98% (Wako Pure Chemical Industries)) 0.1 wt%, polyvinylpyrrolidone (Across organics, molecular weight 3500) 0.1 A solution containing no silver iodide was prepared with wt% and the rest being pure water.
(比較例2)
ヨウ化カリウム(純度KI 99%(和光純薬製))0.5wt%、クエン酸1水和物(純度98%(和光純薬製))1.0wt%、ポリビニルピロリドン(Across organics製、分子量3500)0.1wt%、残りは純水とし、ヨウ化銀を含まない溶液を作成した。
(Comparative example 2)
0.5 wt% potassium iodide (purity KI 99% (Wako Pure Chemical Industries)), citric acid monohydrate (purity 98% (Wako Pure Chemical Industries)) 1.0 wt%, polyvinylpyrrolidone (Across organics, molecular weight 3500) A solution containing no silver iodide was prepared by using 0.1 wt% and pure water as the rest.
(比較例3)
ヨウ化カリウム(純度KI 99%(和光純薬製))1.0wt%、クエン酸1水和物(純度98%(和光純薬製))0.1wt%、ポリビニルピロリドン(Across organics製、分子量3500)0.1wt%、残りは純水とし、ヨウ化銀を含まない溶液を作成した。
(Comparative example 3)
Potassium iodide (Purity KI 99% (Wako Pure Chemical Industries)) 1.0 wt%, citric acid monohydrate (Purity 98% (Wako Pure Chemical Industries)) 0.1 wt%, polyvinylpyrrolidone (Across organics, molecular weight 3500) A solution containing no silver iodide was prepared by using 0.1 wt% and pure water as the rest.
(比較例4)
ヨウ化カリウム(純度KI 99%(和光純薬製))3.0wt%、クエン酸1水和物(純度98%(和光純薬製))0.5wt%、ポリビニルピロリドン(Across organics製、分子量3500)0.1wt%、残りは純水とし、ヨウ化銀を含まない溶液を作成した。
(Comparative example 4)
Potassium iodide (Purity KI 99% (Wako Pure Chemical Industries)) 3.0 wt%, citric acid monohydrate (Purity 98% (Wako Pure Chemical Industries)) 0.5 wt%, polyvinylpyrrolidone (Across organics, molecular weight 3500) A solution containing no silver iodide was prepared by using 0.1 wt% and pure water as the rest.
(比較例5)
実施例1で得られた抗真菌組成物を0.1wt%、ヨウ化カリウム(純度KI 99%(和光純薬製))1.4wt%、クエン酸1水和物(純度98%(和光純薬製))0.1wt%、残りは純水とし、ヨウ化銀の割合が低い組成物を作成した。この組成物の銀イオン:ヨウ化物イオンのモル比率(実施例1の溶液混合時における銀イオン:実施例1の溶液混合時におけるヨウ化物イオンおよび比較例5で新たに添加されたヨウ化カリウム由来のヨウ化物イオンの和)は1:1250であった。ヨウ化銀ナノ粒子の存在は確認できなかった。
(Comparative Example 5)
0.1 wt% of the antifungal composition obtained in Example 1, 1.4 wt% of potassium iodide (purity KI 99% (manufactured by Wako Pure Chemical Industries)), citric acid monohydrate (purity 98% (manufactured by Wako Pure Chemical Industries, Ltd.) )) 0.1 wt% and the rest was pure water to prepare a composition having a low proportion of silver iodide. Molar ratio of silver ion:iodide ion of this composition (silver ion during solution mixing of Example 1: iodide ion during solution mixing of Example 1 and potassium iodide newly added in Comparative Example 5) The sum of iodide ions) was 1:1250. The presence of silver iodide nanoparticles could not be confirmed.
(防カビ試験方法)
真菌は、PDA斜面培地にて培養を行った、白癬菌(Trichophyton mentagrophytes)、を用いた。白癬菌が培養された試験管に、湿潤剤添加滅菌水(0.005% スルホこはく酸ジオクチルナトリウム水溶液)を10ml入れ、白金耳で胞子をかきとった。得られた液を滅菌ガーゼでろ過を行い、胞子が106個/mlになるように湿潤剤添加滅菌水で調整を行い、胞子懸濁液を作成した。48穴マルチプレートに実施例、比較例の各組成物0.5mlと、GP培地0.5mlを入れた。さらに、作成した胞子懸濁液0.1mlを添加し、28℃で1週間培養を行った後、判定を行った。コントロールは、GP培地1mlに胞子懸濁液0.1mlを添加し、同様に培養、判定を行った。判定は、肉眼による真菌の発育の有無により行った。結果を表1に示す。
(Moldproof test method)
The fungus used was Trichophyton mentagrophytes, which was cultured in a PDA slant medium. 10 ml of sterilized water containing a wetting agent (0.005% sodium dioctyl sodium sulfosuccinate solution) was placed in a test tube in which Trichophyton was cultured, and spores were scraped off with a platinum loop. The obtained solution was filtered with sterile gauze and adjusted with sterilized water containing a wetting agent so that the number of spores was 10 6 cells/ml to prepare a spore suspension. A 48-well multiplate was charged with 0.5 ml of each composition of Examples and Comparative Examples and 0.5 ml of GP medium. Further, 0.1 ml of the prepared spore suspension was added, and the cells were cultured at 28° C. for 1 week and then evaluated. As a control, 0.1 ml of spore suspension was added to 1 ml of GP medium, and culture and determination were performed in the same manner. The judgment was made based on the presence or absence of the development of the fungus by the naked eye. The results are shown in Table 1.
以上の結果から、すべての実施例で、白癬菌の生育はみられなかったのに対し、有効成分であるヨウ化銀が含まれていない比較例1では白癬菌の生育がみられた。このことから、本発明の抗真菌組成物は、高い抗真菌性を有する事が確認できた。 From the above results, growth of Trichophyton was not observed in all Examples, whereas growth of Trichophyton was observed in Comparative Example 1 in which silver iodide as an active ingredient was not contained. From this, it was confirmed that the antifungal composition of the present invention has high antifungal properties.
(防カビ試験方法)
真菌は、PDA斜面培地にて培養を行ったクロコウジカビ(Aspergillus niger)、アオカビ(Penicillium pinophilum)、クモノスカビ(Rhizopus oryzae)を用いた。各菌が培養された試験管に、湿潤剤添加滅菌水(0.005% スルホこはく酸ジオクチルナトリウム水溶液)を10ml入れ、白金耳で胞子をかきとった。得られた液を滅菌ガーゼでろ過を行い、胞子が106個/mlになるように湿潤剤添加滅菌水で調整を行い、胞子懸濁液を作成した。48穴マルチプレートに実施例4、比較例4の各組成物0.5mlと、GP培地0.5mlを入れた。さらに、作成した胞子懸濁液0.1mlを添加し、28℃で1週間培養を行った後、判定を行った。コントロールは、GP培地1mlに胞子懸濁液0.1mlを添加し、同様に培養、判定を行った。判定は、肉眼による真菌の発育の有無により行った。結果を表2に示す。
(Moldproof test method)
As the fungi, black mold (Aspergillus niger), blue mold (Penicillium pinophilum), and black mold (Rhizopus oryzae) cultured in a PDA slant medium were used. 10 ml of sterilized water containing a wetting agent (0.005% sodium dioctyl sulfosuccinate aqueous solution) was placed in a test tube in which each bacterium was cultured, and spores were scraped off with a platinum loop. The obtained liquid was filtered with sterile gauze and adjusted with sterilized water containing a wetting agent so that the spores would be 10 6 cells/ml, to prepare a spore suspension. A 48-well multiplate was charged with 0.5 ml of each composition of Example 4 and Comparative Example 4 and 0.5 ml of GP medium. Further, 0.1 ml of the prepared spore suspension was added, and the cells were cultured at 28° C. for 1 week and then evaluated. As a control, 0.1 ml of spore suspension was added to 1 ml of GP medium, and culture and determination were performed in the same manner. The judgment was made based on the presence or absence of the development of the fungus by the naked eye. The results are shown in Table 2.
表1、表2から理解できるとおり、試験に供したすべての実施例で、いずれの真菌についても生育はみられなかったのに対し、有効成分であるヨウ化銀が含まれていない比較例では真菌の生育がみられた。このことから、本発明の抗真菌組成物は、高い抗真菌性を有する事が確認できた。 As can be understood from Table 1 and Table 2, in all of the examples used in the test, no growth was observed in any of the fungi, whereas in Comparative Examples not containing silver iodide as an active ingredient. Fungal growth was observed. From this, it was confirmed that the antifungal composition of the present invention has high antifungal properties.
(防カビ試験方法(定量性試験))
真菌は、PDA斜面培地にて培養を行った、白癬菌(Trichophyton mentagrophytes)、クロカビ(Cladosporium cladosporioides)、アオカビ(Penicillium pinophilum)、クモノスカビ(Rhizopus oryzae)を用いた。各菌が培養された試験管に、湿潤剤添加滅菌水(0.005% スルホこはく酸ジオクチルナトリウム水溶液)を10ml入れ、白金耳で胞子をかきとった。得られた液を滅菌ガーゼでろ過を行い、胞子が106個/mlになるように湿潤剤添加滅菌水で調整を行い、胞子懸濁液を作成した。実施例、コントロールの各組成物1.0mlに胞子懸濁液0.1mlを混合し、一定時間攪拌を行った。各時間後、SCDLP培地により10段階希釈系列を作成した。PDA培地による平板培養法により、生菌数を測定した。結果を表3に示す。
(Moldproof test method (quantitative test))
As the fungus, Trichophyton mentagrophytes, Cladosporium cladosporioides, Penicillium pinophilum, and Rhizopus oryzae cultivated in a PDA slant medium were used. 10 ml of sterilized water containing a wetting agent (0.005% sodium dioctyl sulfosuccinate aqueous solution) was placed in a test tube in which each bacterium was cultured, and spores were scraped off with a platinum loop. The obtained liquid was filtered with sterile gauze and adjusted with sterilized water containing a wetting agent so that the spores would be 10 6 cells/ml, to prepare a spore suspension. 0.1 ml of the spore suspension was mixed with 1.0 ml of each composition of Examples and Control, and stirred for a certain period of time. After each time, a 10-step dilution series was prepared with SCDLP medium. The viable cell count was measured by the plate culture method using PDA medium. The results are shown in Table 3.
以上の結果から、すべての真菌において、30分で生菌数が検出限界以下になることが確認できた。このことから、本発明の抗真菌組成物は、殺カビ効果があることも確認できた。 From the above results, it was confirmed that the number of viable bacteria was below the detection limit in 30 minutes for all fungi. From this, it was also confirmed that the antifungal composition of the present invention has a fungicidal effect.
Claims (2)
前記ハロゲン化銀を構成するハロゲンと同元素のハロゲン化物イオンと、
少なくとも1種の水溶性高分子と、
カルボキシル基を有する有機酸および/またはその塩とを含み、
前記ハロゲン化銀中の銀と前記ハロゲン化物イオンとのモル比が1:10〜1:1000であり、
前記ハロゲン化銀からなるナノ粒子の周囲に電気二重層が形成されていることを特徴とする抗真菌組成物。 Nanoparticles composed of silver halide having a particle size of 1 nm or more and less than 10 nm,
A halide ion of the same element as the halogen constituting the silver halide,
At least one water-soluble polymer,
An organic acid having a carboxyl group and/or a salt thereof,
The molar ratio of silver and the halide ions in the silver halide is 1: 10 to 1: Ri 1000 der,
An antifungal composition characterized in that an electric double layer is formed around the silver halide nanoparticles .
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