JP5083907B2 - Gel-like antibacterial agent - Google Patents
Gel-like antibacterial agent Download PDFInfo
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- JP5083907B2 JP5083907B2 JP2008323823A JP2008323823A JP5083907B2 JP 5083907 B2 JP5083907 B2 JP 5083907B2 JP 2008323823 A JP2008323823 A JP 2008323823A JP 2008323823 A JP2008323823 A JP 2008323823A JP 5083907 B2 JP5083907 B2 JP 5083907B2
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- antibacterial agent
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Description
本発明は抗菌剤、好適にはゲル状で用いられる抗菌剤に関する。本発明の抗菌剤は、グラム陽性菌および陰性菌の双方に対して抗菌性を有するため、広範な用途で抗菌剤として用いることができる。 The present invention relates to an antibacterial agent, preferably an antibacterial agent used in a gel form. Since the antibacterial agent of the present invention has antibacterial properties against both gram-positive and negative bacteria, it can be used as an antibacterial agent in a wide range of applications.
従来から、ゲルを形成する水溶性ゲル化剤、特に、カルボキシビニルポリマーを用いた抗菌ゲル製剤は医薬品等に使用されてきた。（例えば、特許文献１，２参照）
また、抗菌薬剤を水溶性ゲル化剤および低級アルコールに添加し、これに抗菌力を不活性化しない粉末と、油分とを配合することで、ゲル状抗菌剤を調製することも知られている。（特許文献３参照）
しかし、単独の電解質化合物を用いて、水性溶媒を含有するゲル状抗菌剤を作製した例はなかった。
It is also known to prepare a gel-like antibacterial agent by adding an antibacterial agent to a water-soluble gelling agent and a lower alcohol, and blending this with a powder that does not inactivate antibacterial activity and an oil. . (See Patent Document 3)
However, there has been no example of producing a gel-like antibacterial agent containing an aqueous solvent using a single electrolyte compound.
本発明は、従来の技術における上記した実状に鑑みてなされたものである。すなわち、本発明の目的は、単独の電解質化合物を用いて、水性溶媒を含有するゲル状抗菌剤を提供することにある。 This invention is made | formed in view of the above-mentioned actual condition in a prior art. That is, an object of the present invention is to provide a gel-like antibacterial agent containing an aqueous solvent using a single electrolyte compound.
本発明者等は、先に電解質であるピリジニウム構造を持つ新規なゲル化剤を開発し、特許出願をした（特許文献４）。他方、塩化ベンザルコニウムに代表される、ある種のアンモニウム化合物は、抗菌性を有することが既に広く知られている。本発明者等はこれらの知見に基づき、先に開発したピリジニウム電解質の抗菌剤としての機能に着目して、本発明を完成するに至った。
すなわち、本発明は、下記一般式（１）で表される化合物及び水性溶媒を含有するゲル状抗菌剤を提供するものである。
本発明のゲル状抗菌剤は、グラム陰性菌及びグラム陽性菌に対して良好な抗菌性を示す。また、濃度を調整することによってゲル状の抗菌剤とすることができ、医薬、化粧品分野などにおける抗菌性保湿剤などとして、有用である。 The gel-like antibacterial agent of the present invention exhibits good antibacterial properties against gram-negative and gram-positive bacteria. Moreover, it can be made into a gel-like antibacterial agent by adjusting the concentration, and is useful as an antibacterial moisturizing agent in the pharmaceutical and cosmetic fields.
本発明の一般式（１）で表わされる化合物及び水性溶媒を含有するゲル状抗菌剤は、当該化合物と水性溶媒を一定の割合で混合することによって調製される。
水性溶媒としては、水及び、水とメタノールやエタノールのような、水溶性溶媒との混合物を使用することができる。
The gel-like antibacterial agent containing the compound represented by the general formula (1) of the present invention and an aqueous solvent is prepared by mixing the compound and the aqueous solvent in a certain ratio.
As the aqueous solvent, water and a mixture of water and a water-soluble solvent such as methanol or ethanol can be used.
本発明のゲル状抗菌剤における一般式（１）で表される化合物の配合量は特に制限がなく、水性溶媒に対し1x10-3〜10質量％が好適であり、好ましくは0.5〜5質量％、特に好ましくは1〜3質量％である。 There is no restriction | limiting in particular in the compounding quantity of the compound represented by General formula (1) in the gel-like antibacterial agent of this invention, 1x10 < -3 > -10 mass% is suitable with respect to an aqueous solvent, Preferably it is 0.5-5 mass% Particularly preferably, it is 1 to 3% by mass.
上記一般式（１）で表される化合物は、例えばアミノピリジン類と活性メチレン基を分子内に持つ安息香酸クロライドとを用いて、下記の反応式に従ってアミド化反応およびそれに続く４級化反応により得ることができる。
この反応は、好ましくは、トリエチルアミンの存在下に、反応成分を有機溶媒に溶解させて、攪拌することにより進行する。有機溶媒としては、エーテル類、炭化水素類、塩素を含む炭化水素類等が使用できるが、クロロメチル安息香酸クロライドの分解を抑え、反応を制御するためには、塩素原子を含む炭化水素類等、特に塩化メチレンが好ましい。反応温度としては０〜１００℃の範囲が好ましく、２０〜４０℃がより好ましい。また、反応時間は反応温度に依存するが、通常は１２〜５０時間程度である。 This reaction preferably proceeds by dissolving the reaction components in an organic solvent and stirring in the presence of triethylamine. As organic solvents, ethers, hydrocarbons, hydrocarbons containing chlorine, etc. can be used, but in order to suppress the decomposition of chloromethylbenzoic acid chloride and control the reaction, hydrocarbons containing chlorine atoms, etc. In particular, methylene chloride is preferred. As reaction temperature, the range of 0-100 degreeC is preferable, and 20-40 degreeC is more preferable. The reaction time depends on the reaction temperature, but is usually about 12 to 50 hours.
以下、本発明を実施例等によりさらに具体的に説明するが、本発明はこれらの実施例によって何ら限定されるものではない。 EXAMPLES Hereinafter, although an Example etc. demonstrate this invention further more concretely, this invention is not limited at all by these Examples.
（製造例１）
４−アミノピリジン４．２７ｇ（４５．３ｍｍｏｌ）と４−（クロロメチル）安息香酸クロライド８．３４ｇ（４５．３ｍｍｏｌ）を、トリエチルアミン６．９５ｍＬ（４９．９ｍｍｏｌ）の存在下に、無水ジクロロメタン１００ｍＬ中で混合し、室温で一晩攪拌したところ、白色沈殿が生成した。これを濾過することにより、上記反応式に従って、下記式（１）で表される化合物９．５１ｇを得た。（収率８５％）
4.27 g (45.3 mmol) of 4-aminopyridine and 8.34 g (45.3 mmol) of 4- (chloromethyl) benzoic acid chloride in 100 mL of anhydrous dichloromethane in the presence of 6.95 mL (49.9 mmol) of triethylamine And stirred at room temperature overnight, a white precipitate formed. By filtering this, 9.51 g of a compound represented by the following formula (1) was obtained according to the above reaction formula. (Yield 85%)
質量分析の結果、ｎは２〜３０の整数であった。また、化学構造は、希薄溶液（重水）の１ＨＮＭＲより、ベンジルピリジニウム塩に特徴的な低磁場シフトしたメチレンのピーク（約６ ｐｐｍ）が観測されたことによって、確認した。
ＮＭＲデータ（３００ＭＨｚ，Ｄ２Ｏ）：δ ５．８３（Ｐｈ−ＣＨ２−Ｎ＋，２Ｈ），７．６６（２Ｈ），８．０５（２Ｈ），８．３１（２Ｈ），８．７７（２Ｈ）
As a result of mass spectrometry, n was an integer of 2 to 30. The chemical structure was confirmed by the observation of a low-field-shifted methylene peak (about 6 ppm) characteristic of benzylpyridinium salts from 1 HNMR of dilute solution (heavy water).
NMR data (300 MHz, D 2 O): δ 5.83 (Ph—CH 2 —N + , 2H), 7.66 (2H), 8.05 (2H), 8.31 (2H), 8.77 (2H)
（実施例）
上記製造例１で得られた、一般式（１）で表わされる化合物が１重量％程度の濃度になるように、中性の脱イオン水と混合し加熱すると、８０℃付近で溶液が透明になり無色均一溶液となった。これを室温に放冷し５分間程度経過すると、安定な半透明のハイドロゲルが生成した。このゲルを、さらに滅菌精製水で希釈することにより、種々の濃度の水溶液を調製した。
(Example)
When the compound represented by the general formula (1) obtained in Production Example 1 is mixed with neutral deionized water and heated so as to have a concentration of about 1% by weight, the solution becomes transparent at around 80 ° C. A colorless homogeneous solution was obtained. When this was allowed to cool to room temperature and about 5 minutes passed, a stable translucent hydrogel was formed. The gel was further diluted with sterilized purified water to prepare aqueous solutions of various concentrations.
（抗菌性試験）
得られた溶液の抗菌性を、日本化学療法学会標準法に準じて，つぎのようにして行った。
試験菌前培養用培地としてTriptic Soy Agar (Difro)、試験菌調製液として、滅菌生理食塩水、感受性測定用培地として、Mueller-Hinton broth (BBL)を用いた。まず、試験菌調製液として凍結保存された菌株を、適温（菌種によって35±1℃もしくは30±1℃）で24時間継代培養した。発育したコロニーをかき取り、試験菌調製液に懸濁後、脱脂綿でろ過した。菌数を約 107 CFU/ml（CFU: colony forming unit）に調製し、試験菌液とした。
前記と同様に、滅菌精製水で1024μg/mLに希釈した試験品 0.8mLを滅菌イオン交換水0.8mLに加えて 2倍希釈した。以下同様に2倍希釈を繰り返し、試験品希釈列を合計10段階作成した(試験品濃度：512、256、128、64、32、16、8、4、2、l μg/mL)。培地の混合は、あらかじめ分注しておいた 2倍濃度の感受性測定用培地と試験品希釈列の各液を等量混合し、2倍希釈した(試験品濃度：256、128、64、32、16、8、4、2、1、0.5 μg/ mL)。このときの培地濃度は通常濃度となる。これら培地と混合した試験品希釈列をU字型ウエルのマイクロプレートに0.1 mLずつ必要列分注した。
(Antimicrobial test)
The antibacterial properties of the obtained solution were determined as follows according to the standard method of the Japanese Society of Chemotherapy.
Triptic Soy Agar (Difro) was used as a pre-culture medium for test bacteria, sterile physiological saline was used as a test bacteria preparation, and Mueller-Hinton broth (BBL) was used as a medium for sensitivity measurement. First, a strain that was cryopreserved as a test bacterium preparation solution was subcultured at an appropriate temperature (35 ± 1 ° C. or 30 ± 1 ° C. depending on the bacterial species) for 24 hours. The grown colonies were scraped off, suspended in the test bacterium preparation solution, and filtered through absorbent cotton. The number of bacteria was adjusted to about 10 7 CFU / ml (CFU: colony forming unit) and used as a test bacterial solution.
In the same manner as described above, 0.8 mL of a test product diluted to 1024 μg / mL with sterilized purified water was added to 0.8 mL of sterilized ion-exchanged water and diluted 2-fold. Thereafter, the 2-fold dilution was repeated in the same manner to prepare a total of 10 test sample dilution columns (test product concentrations: 512, 256, 128, 64, 32, 16, 8, 4, 2, l μg / mL). The medium was mixed in the same amount with each of the two-fold concentration measuring medium for sensitivity measurement and the test product dilution column that had been dispensed in advance and diluted twice (test product concentration: 256, 128, 64, 32). 16, 8, 4, 2, 1, 0.5 μg / mL). The medium concentration at this time is a normal concentration. The required dilution series of the test product mixed with these media was dispensed in 0.1 mL each into a U-shaped well microplate.
抗菌試験操作は、マイクロプレートの各ウェルに試験菌液を5 Lずつ滴下し、24時間適温（菌種によって35±1℃もしくは30±1℃）で培養した。陰性 controlを対照として、菌発育の有無を肉眼で判定し、発育の見られない最小濃度をM IC値とした。その結果、表１に示すMIC値で、グラム陽性菌およびグラム陰性菌の双方に対する抗菌性を示した。 In the antibacterial test operation, 5 L of the test bacterial solution was dropped into each well of the microplate and cultured at an appropriate temperature (35 ± 1 ° C. or 30 ± 1 ° C. depending on the bacterial species) for 24 hours. Using negative control as a control, the presence or absence of bacterial growth was determined with the naked eye, and the minimum concentration at which no growth was observed was defined as the MIC value. As a result, the MIC values shown in Table 1 showed antibacterial properties against both gram-positive and gram-negative bacteria.
上記表１に見られるように、本発明の一般式（１）で表される化合物及び水性溶媒を含有する抗菌剤は、グラム陰性菌及びグラム陽性菌に対して良好な抗菌性を示した。
本発明の抗菌剤は、一般式（１）で表される化合物の濃度を調整することによって、ゲル状抗菌剤とすることができ、各種の化粧品、ハンドクリーム、衛生用品等に好適に用いることができる。
As seen in Table 1 above, the antibacterial agent containing the compound represented by the general formula (1) of the present invention and the aqueous solvent showed good antibacterial properties against Gram-negative bacteria and Gram-positive bacteria.
The antibacterial agent of the present invention can be made into a gel-like antibacterial agent by adjusting the concentration of the compound represented by the general formula (1), and is preferably used for various cosmetics, hand creams, hygiene products, and the like. Can do.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| JP2008323823A JP5083907B2 (en) | 2008-12-19 | 2008-12-19 | Gel-like antibacterial agent |
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| JP2008323823A JP5083907B2 (en) | 2008-12-19 | 2008-12-19 | Gel-like antibacterial agent |
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| JP2010143869A JP2010143869A (en) | 2010-07-01 |
| JP5083907B2 true JP5083907B2 (en) | 2012-11-28 |
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| CN114318574B (en) * | 2022-01-25 | 2022-09-13 | 深圳市记忆时候科技有限公司 | Antibacterial antiviral mildew-proof textile and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS58154502A (en) * | 1982-03-10 | 1983-09-14 | Nariaki Kawabata | Agent for controlling microorganism |
| JPH04164035A (en) * | 1990-10-29 | 1992-06-09 | Kao Corp | Microorganism adsorbent and production thereof |
| US20030021761A1 (en) * | 2001-01-18 | 2003-01-30 | Geltex Pharmaceuticals, Inc. | Ionene polymers and their use in treating mucositis |
| JP4588034B2 (en) * | 2004-12-16 | 2010-11-24 | 日本曹達株式会社 | Novel bis-quaternary ammonium salt compound having bactericidal activity |
| JP4934797B2 (en) * | 2005-02-02 | 2012-05-16 | 独立行政法人産業技術総合研究所 | Ionic organic compounds |
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