JP2019034921A - Bactericidal and antibacterial composition - Google Patents
Bactericidal and antibacterial composition Download PDFInfo
- Publication number
- JP2019034921A JP2019034921A JP2017166172A JP2017166172A JP2019034921A JP 2019034921 A JP2019034921 A JP 2019034921A JP 2017166172 A JP2017166172 A JP 2017166172A JP 2017166172 A JP2017166172 A JP 2017166172A JP 2019034921 A JP2019034921 A JP 2019034921A
- Authority
- JP
- Japan
- Prior art keywords
- copper
- group
- chelate complex
- solution
- antibacterial
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 17
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 36
- 239000010949 copper Substances 0.000 claims abstract description 34
- 230000001954 sterilising effect Effects 0.000 claims abstract description 29
- 229910052802 copper Inorganic materials 0.000 claims abstract description 27
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910001431 copper ion Inorganic materials 0.000 claims abstract description 16
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims abstract description 15
- -1 copper chelate complex Chemical class 0.000 claims abstract description 15
- URDCARMUOSMFFI-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(2-hydroxyethyl)amino]acetic acid Chemical compound OCCN(CC(O)=O)CCN(CC(O)=O)CC(O)=O URDCARMUOSMFFI-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000004659 sterilization and disinfection Methods 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 7
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001340 alkali metals Chemical class 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 6
- 125000002091 cationic group Chemical group 0.000 claims description 6
- 239000002738 chelating agent Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 abstract description 3
- 238000010586 diagram Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 19
- 239000007864 aqueous solution Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 241000588724 Escherichia coli Species 0.000 description 8
- 239000013522 chelant Substances 0.000 description 8
- 238000007865 diluting Methods 0.000 description 7
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 239000012085 test solution Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 4
- 102000004856 Lectins Human genes 0.000 description 4
- 108090001090 Lectins Proteins 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000005018 casein Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000002523 lectin Substances 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000000536 complexating effect Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 239000005749 Copper compound Substances 0.000 description 1
- JJLJMEJHUUYSSY-UHFFFAOYSA-L Copper hydroxide Chemical compound [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 description 1
- 239000005750 Copper hydroxide Substances 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- BFMRUPBDRCFGEB-UHFFFAOYSA-N O.O.[Na].[Na].[Na] Chemical compound O.O.[Na].[Na].[Na] BFMRUPBDRCFGEB-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001880 copper compounds Chemical class 0.000 description 1
- 229910001956 copper hydroxide Inorganic materials 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
【課題】高い殺菌・抗菌効果を発揮し、安全で安定的な殺菌・抗菌用組成物を提供する。【解決手段】殺菌・抗菌用組成物は、銅イオンをエチレンジアミン四酢酸（ＥＤＴＡ）又は、Ｎ−（２−ヒドロキシエチル）エチレンジアミン−Ｎ，Ｎ’，Ｎ’−三酢酸（ＨＥＤＴＡ）の少なくともいずれか一つで、銅キレート錯体とした塩を用いることで銅イオンを安定化し、人体に対して安全に作用させることを特徴とする。【選択図】なし[Problem] To provide a safe and stable sterilizing and antibacterial composition that exhibits high sterilizing and antibacterial effects. [Solution] The sterilizing/antibacterial composition includes copper ions in at least one of ethylenediaminetetraacetic acid (EDTA) and N-(2-hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid (HEDTA). One feature is that copper ions are stabilized by using a salt in the form of a copper chelate complex, making them safe for the human body. [Selection diagram] None
Description
本発明は、殺菌・抗菌用組成物に関する。 The present invention relates to a bactericidal / antibacterial composition.
銅の殺菌・抗菌作用は昔から知られている。この銅の殺菌・抗菌作用を利用して様々な商品が考案されている。銅金属をそのまま使用できる場合であれば良いが、液体として使用する場合には、銅イオンとして作用させなければならず、銅イオンを単独で溶液中に長時間、留めておくことは困難で、時間経過と共に水酸化銅の形で沈殿してしまう。銅イオンは、１９８５年に文部省「環境科学」特別研究人体影響班によるサルでの長期実験で安全性が確認されている。 The antibacterial and antibacterial action of copper has been known for a long time. Various products have been devised using the sterilization and antibacterial action of copper. It is sufficient if copper metal can be used as it is, but when used as a liquid, it must act as copper ions, and it is difficult to keep copper ions alone in the solution for a long time, It will precipitate in the form of copper hydroxide over time. In 1985, copper ions were confirmed to be safe in a long-term experiment in monkeys by the Ministry of Education's “Environmental Science” Special Research Human Body Impact Group.
しかしながら、従来の方法では、銅イオン単独では、銅イオンの存在が不安定なため、殺菌・抗菌効果が不十分な場合があり、より効果で、安全で新たな殺菌・抗菌用組成物が求められている。特許文献１に記載の技術は、金属塩として用いるため、殺菌力が低く、安定性に問題がある。また、特許文献２も金属化合物とキレート剤を別に使用しているため、殺菌力と安定性に問題がある。また更に、特許文献３においては、銅化合物と過酸化水素を含有することとなっているため、人体に直接的に使用するにあたって、安全性に欠ける。 However, in the conventional method, since the presence of copper ions alone is unstable, the sterilization / antibacterial effect may be insufficient in some cases, and a more effective, safe and new sterilization / antibacterial composition is desired. It has been. Since the technique described in Patent Document 1 is used as a metal salt, the sterilizing power is low and there is a problem in stability. Moreover, since patent document 2 uses the metal compound and the chelating agent separately, there exists a problem in bactericidal power and stability. Furthermore, in patent document 3, since it contains a copper compound and hydrogen peroxide, when using it directly to a human body, it lacks safety.
本発明は、上記事情に鑑みてなされたものであり、銅イオンとしての高い殺菌・抗菌効果を発揮し、かつ、安定性に優れ、人体に安全な殺菌・抗菌用組成物を提供することを課題とする。 The present invention has been made in view of the above circumstances, and provides a sterilization / antibacterial composition that exhibits high sterilization / antibacterial effects as copper ions, has excellent stability, and is safe for the human body. Let it be an issue.
本発明の殺菌・抗菌用組成物は、銅イオンとのキレート剤が、下記、一般式（Ｉ）または（ＩＩ）の少なくともいずれか一つで、銅キレート錯体として含有することを特徴とする。 The sterilizing / antibacterial composition of the present invention is characterized in that the chelating agent with copper ions is at least one of the following formulas (I) or (II) and is contained as a copper chelate complex.
（式中、Ｘ１〜Ｘ４は同一でも異なっていてもよく、それぞれ水素原子、アルカリ金属、アルカリ土類金属、カチオン性アンモニウム基からなる群より選ばれる１種を表している。）
（式中、Ｙはアルキル基、カルボキシル基、スルホ基、アミノ基、水酸基、または水素原子を表し、Ｘ５〜Ｘ７は同一でも異なっていてもよく、それぞれ水素原子、アルカリ金属、アルカリ土類金属、カチオン性アンモニウム基からなる群より選ばれる１種を表し、ｎは０から５の整数を表す。）(In the formula, Y represents an alkyl group, a carboxyl group, a sulfo group, an amino group, a hydroxyl group, or a hydrogen atom, and X5 to X7 may be the same or different, and each represents a hydrogen atom, an alkali metal, an alkaline earth metal, This represents one selected from the group consisting of cationic ammonium groups, and n represents an integer of 0 to 5.)
本発明によれば、銅イオンとしての高い殺菌・抗菌効果を発揮し、かつ、安定性に優れ、人体に安全な殺菌・抗菌用組成物を提供することができる。 ADVANTAGE OF THE INVENTION According to this invention, the high bactericidal and antibacterial effect as a copper ion is exhibited, it is excellent in stability, and the composition for bactericidal and antibacterial safe to a human body can be provided.
生体中におけるウイルス及び細菌感染による炎症部位では、白血球が作用し、感染部位においてウイルス及び細菌と白血球との接近部位では強酸性を呈し、全体としてその炎症部位は酸性を呈する。 Leukocytes act at sites of inflammation due to viral and bacterial infections in the body, and strong acidity is exhibited at sites where the virus, bacteria, and leukocytes are approached at the sites of infection, and the site of inflammation as a whole exhibits acidity.
また、一般式（Ｉ）または（ＩＩ）の水溶液中で陰イオンとなる−ＣＯＯ−の部分が酸性下においてはキレート能が低下する。In general formula (I) or a negative ion in an aqueous solution of (II) -COO - moiety of the chelating ability is reduced under acidic conditions.
そのため、炎症部位においては、該銅キレート錯体のキレート能が低下して、銅イオンがキレート剤から解放される。 Therefore, at the inflammatory site, the chelating ability of the copper chelate complex decreases, and copper ions are released from the chelating agent.
炎症が起こっている酸性部位でキレートが解かれ、銅イオンが炎症部位でウイルス及び細菌に対して殺菌や抗菌の作用をする。よって、該銅レート錯体による殺菌・抗菌用組成物を提供することができる。 Chelates are released at acidic sites where inflammation is occurring, and copper ions act as bactericides and antibacterials against viruses and bacteria at the sites of inflammation. Therefore, a composition for sterilization and antibacterial using the copper rate complex can be provided.
以下、本発明を詳細に説明する。
本発明の殺菌・抗菌用組成物は、銅イオンのキレート剤として、下記一般式（Ｉ）または（ＩＩ）のいずれかの構造の化合物（以下、化合物（Ａ）、（Ｂ）という。）であることを特徴とする。Hereinafter, the present invention will be described in detail.
The antibacterial / antibacterial composition of the present invention is a compound having a structure of any one of the following general formulas (I) or (II) (hereinafter referred to as compounds (A) and (B)) as a chelating agent for copper ions. It is characterized by being.
化合物（Ａ）は、下記一般式（Ｉ）で示される。 The compound (A) is represented by the following general formula (I).
化合物（Ａ）において、Ｘ１〜Ｘ４は同一でも異なっていてもよく、それぞれ水素原子、アルカリ金属、アルカリ土類金属、カチオン性アンモニウム基からなる群より選ばれる１種を表す。
Ｘ１〜Ｘ４が上記のものであると、本発明の殺菌・除菌用組成物を水に溶解すると、この化合物（Ａ）は、−ＣＯＯＸ１、−ＣＯＯＸ２、−ＣＯＯＸ３、−ＣＯＯＸ４が電離して、それぞれ−ＣＯＯ−となり、陰イオンを生成する。そして、この陰イオンの−ＣＯＯ−の部分が銅元素と錯形成可能となる。
好ましくは、Ｘ１〜Ｘ４はいずれもナトリウムまたはカリウムである。なお、Ｘ１〜Ｘ４のうちの１種以上がアルカリ土類金属Ｍである場合には、その部分は−ＣＯＯＭと示されることとなる。In the compound (A), X1 to X4 may be the same or different, and each represents one selected from the group consisting of a hydrogen atom, an alkali metal, an alkaline earth metal, and a cationic ammonium group.
When the sterilizing / sterilizing composition of the present invention is dissolved in water when X1 to X4 are as described above, this compound (A) is ionized by -COOX1, -COOX2, -COOX3, -COOX4, each -COO - next, to generate the anion. Then, the anionic -COO - moiety is elemental copper and the complexing possible.
Preferably, X1 to X4 are all sodium or potassium. When at least one of X1 to X4 is an alkaline earth metal M, the part is represented as -COOM.
化合物（Ａ）の具体例としては、エチレンジアミン四酢酸二水素二ナトリウムなどが挙げられる。 Specific examples of the compound (A) include disodium ethylenediaminetetraacetate and the like.
化合物（Ｂ）は、下記一般式（ＩＩ）で示される。 The compound (B) is represented by the following general formula (II).
化合物（Ｂ）において、Ｙはアルキル基、カルボキシル基、スルホ基、アミノ基、水酸基、または水素原子を表し、Ｘ５〜Ｘ７は同一でも異なっていてもよく、それぞれ水素原子、アルカリ金属、アルカリ土類金属、カチオン性アンモニウム基からなる群より選ばれる１種を表す。
Ｘ５〜Ｘ７が上記のものである場合、本発明の殺菌・除菌用組成物を洗濯時に水に溶解すると、この化合物（Ｂ）は、−ＣＯＯＸ５、−ＣＯＯＸ６、−ＣＯＯＸ７が電離して、それぞれ−ＣＯＯ−となり、陰イオンを生成する。そして、この陰イオンの−ＣＯＯ−の部分が銅元素と錯形成可能となる。
好ましくは、Ｘ５〜Ｘ７はいずれもナトリウムまたはカリウムである。なお、Ｘ５〜Ｘ７のうちの１種以上がアルカリ土類金属Ｍである場合には、その部分は−ＣＯＯＭと示されることとなる。また、ｎは０から５の整数を表し、好ましくは０から２である。In the compound (B), Y represents an alkyl group, a carboxyl group, a sulfo group, an amino group, a hydroxyl group, or a hydrogen atom, and X5 to X7 may be the same or different, and each represents a hydrogen atom, an alkali metal, or an alkaline earth. 1 type chosen from the group which consists of a metal and a cationic ammonium group.
When X5 to X7 are as described above, when the sterilizing / sterilizing composition of the present invention is dissolved in water during washing, this compound (B) is ionized by -COOX5, -COOX6, -COOX7, -COO - next, to generate the anion. Then, the anionic -COO - moiety is elemental copper and the complexing possible.
Preferably, all of X5 to X7 are sodium or potassium. When at least one of X5 to X7 is an alkaline earth metal M, the part is represented as -COOM. N represents an integer of 0 to 5, preferably 0 to 2.
化合物（Ｂ）の具体例としては、Ｎ−（２−ヒドロキシエチル）エチレンジアミン−Ｎ，Ｎ’，Ｎ’−三酢酸三ナトリウムなどが挙げられる。 Specific examples of the compound (B) include N- (2-hydroxyethyl) ethylenediamine-N, N ′, N′-trisodium triacetate.
なお、殺菌効果とは、表面に存在する菌数を減少させる効果を示し、抗菌効果とは、表面に付着した菌の増殖を抑制する効果を示す。 The bactericidal effect refers to the effect of reducing the number of bacteria present on the surface, and the antibacterial effect refers to the effect of suppressing the growth of bacteria attached to the surface.
銅イオンをエチレンジアミン四酢酸（ＥＤＴＡ）又は、Ｎ−（２−ヒドロキシエチル）エチレンジアミン−Ｎ，Ｎ’，Ｎ’−三酢酸（ＨＥＤＴＡ）の少なくともいずれか一つで、銅キレート錯体とした塩は、銅が抗菌組成物中に６２５ｐｐｍ以上となるように配合すると好ましく、１０００ｐｐｍ以上であると更に好ましく、１２５０ｐｐｍ以上であると特に好ましい。 A salt in which the copper ion is at least one of ethylenediaminetetraacetic acid (EDTA) or N- (2-hydroxyethyl) ethylenediamine-N, N ′, N′-triacetic acid (HEDTA) and is a copper chelate complex, It is preferable that copper is blended in the antibacterial composition so as to be 625 ppm or more, more preferably 1000 ppm or more, and particularly preferably 1250 ppm or more.
該銅キレート錯体の作用場のｐＨ値は、０〜６．０が好ましく、０〜４．０であると更に好ましい。 The pH value of the action field of the copper chelate complex is preferably 0 to 6.0, and more preferably 0 to 4.0.
下記に錯体化の具体的方法の例について説明するが、特に制限されるものではない。 Although the example of the concrete method of complexation is demonstrated below, it does not restrict | limit in particular.
実施例１
＜エチレンジアミン四酢酸（ＥＤＴＡ）銅キレート錯体水溶液作成＞
既に銅イオンとエチレンジアミン四酢酸（ＥＤＴＡ）でキレートされているキレストＣｕ（キレスト株式会社製）を用いて調整し作成した溶液を作成する。
水はイオン交換水を用いた。
銅濃度として、
（Ａ−１）２００ｐｐｍは、
キレストＣｕを０．１６ｇ取り、を注入して１００ｍｌとする溶液。
（Ｂ−１）５００ｐｐｍは、
キレストＣｕを０．４ｇ取り、水を注入して１００ｍｌとする溶液。
（Ｃ−１）６２５ｐｐｍは、
キレストＣｕを０．５ｇ取り、水を注入して１００ｍｌとする溶液。
（Ｄ−１）１０００ｐｐｍは、
キレストＣｕを０．８ｇ取り、水を注入して１００ｍｌとする溶液。
（Ｅ−１）１２５０ｐｐｍは、
キレストＣｕを１．０ｇ取り、水を注入して１００ｍｌとする溶液。
（Ｆ−１）１５００ｐｐｍは、
キレストＣｕを１．２ｇ取り、水を注入して１００ｍｌとする溶液。
をそれぞれ作成した。Example 1
<Creation of ethylenediaminetetraacetic acid (EDTA) copper chelate complex aqueous solution>
A solution prepared by adjusting with the use of Kirest Cu (manufactured by Kirest Co., Ltd.) already chelated with copper ion and ethylenediaminetetraacetic acid (EDTA) is prepared.
Water used was ion exchange water.
As copper concentration,
(A-1) 200 ppm is
A solution in which 0.16 g of chilles Cu is taken and 100 ml is injected.
(B-1) 500 ppm is
A solution that takes 0.4 g of chilles Cu and injects water to make 100 ml.
(C-1) 625 ppm is
A solution that takes 0.5 g of chilles Cu and injects water to make 100 ml.
(D-1) 1000 ppm is
A solution that takes 0.8 g of chilles Cu and injects water to make 100 ml.
(E-1) 1250 ppm is
A solution in which 1.0 g of chillest Cu is taken and water is poured to make 100 ml.
(F-1) 1500 ppm is
A solution that takes 1.2 g of Kirest Cu and injects water to make 100 ml.
Was created respectively.
＜ｐＨ３．０の希塩酸作成＞
ｐＨメーターで測定しながら、１００ｍＬのイオン交換水に１Ｎの塩酸をパスツールピペットで１滴ずつ入れていきｐＨ３．０の塩酸を作成する。<Preparation of dilute hydrochloric acid with pH 3.0>
While measuring with a pH meter, 1N hydrochloric acid is added dropwise to 100 mL of ion exchange water with a Pasteur pipette to prepare hydrochloric acid having a pH of 3.0.
大腸菌は、酸に対して非常に耐性が高い、そのため酸性下の殺菌力評価に大腸菌を用いた。 Escherichia coli is very resistant to acids, and therefore E. coli was used for evaluation of bactericidal activity under acidic conditions.
「殺菌力評価」
殺菌・抗菌用組成物が、銅濃度といて、比較例は０質量％、上記で調整した（Ａ−１）、（Ｂ−１）、（Ｃ−１）、（Ｄ−１）、（Ｅ−１）、（Ｆ−１）の溶液から試験液として８．９ｍＬをそれぞれ取り、ｐＨ３．０の希塩酸１ｍＬを各試験液に加え、さらに各試験液へ菌数が１００個／ｍＬとなるように調整された大腸菌母液（ＩＦＯ３９７２）０．１ｍＬを添加し、均一に攪拌した。１０分後に１ｍＬ採取し、９ｍＬのＳＣＤＬＰ培地（Ｓｏｙｂｅａｎ−Ｃａｓｅｉｎ Ｄｉｇｅｓｔ Ｂｒｏｔｈ ｗｉｔｈ Ｌｅｃｔｉｎ ＆ Ｐｏｌｙｓｏｒｂａｔｅ ８０：和光純薬工業株式会社製）に加え、１０倍希釈液とした。得られた希釈液をさらに１０倍に希釈する操作を４回繰り返し、１０倍から１０００００倍の希釈を得た。これら各希釈液から１．０ｍＬをシャーレに採取し、ＳＣＤＬＰ寒天培地（Ｓｏｙｂｅａｎ−Ｃａｓｅｉｎ Ｄｉｇｅｓｔ Ａｇｅｒ ｗｉｔｈ Ｌｅｃｔｉｎ ＆ Ｐｏｌｙｓｏｒｂａｔｅ ８０：和光純薬工業株式会社製）１５ｍＬを加えて均一化し、３７℃で２日間培養した後、コロニー数７０〜３００の範囲にあるものを選んでコロニーをカウントして生存菌数を求め、初菌数の対数値と試験後の生存菌数の対数値との差を殺菌数とした。"Bactericidal evaluation"
The composition for sterilization / antibacterial is copper concentration, and the comparative example is 0% by mass, adjusted as described above (A-1), (B-1), (C-1), (D-1), (E -1) Take 8.9 mL of the test solution from the solution of (F-1), add 1 mL of dilute hydrochloric acid of pH 3.0 to each test solution, and further increase the number of bacteria to 100 / mL in each test solution. 0.1 mL of the Escherichia coli mother liquor (IFO3972) prepared in the above was added and stirred uniformly. After 10 minutes, 1 mL was collected and added to 9 mL of SCDLP medium (Soybean-Casein Digest Broth With Lectin & Polysorbate 80: manufactured by Wako Pure Chemical Industries, Ltd.) to give a 10-fold dilution. The operation of further diluting the obtained diluted solution 10 times was repeated 4 times to obtain 10 times to 100,000 times dilution. Collect 1.0 mL from each of these dilutions in a petri dish, add 15 mL of SCDLP agar medium (Soybean-Casein Digest Age with Lectin & Polysorbate 80: Wako Pure Chemical Industries, Ltd.), homogenize, and culture at 37 ° C. for 2 days After that, the number of colonies in the range of 70-300 is selected and the number of colonies is counted to determine the number of surviving bacteria. did.
（殺菌力評価基準）
比較例の場合と比較して、以下の４段階で殺菌力を評価した。
・大腸菌に対する抗菌効果基準
×：殺菌数１桁未満。
△：殺菌数２桁未満。
○：殺菌数２桁以上だが、全滅には至らない。
◎：残存菌数０（全滅）。
結果を表１に示す。(Sterilization power evaluation criteria)
Compared to the comparative example, the sterilizing power was evaluated in the following four stages.
-Antibacterial effect standard against E. coli ×: Number of sterilizations is less than one digit.
Δ: The number of sterilizations is less than 2 digits.
○: The number of sterilization is 2 digits or more, but it is not annihilated.
A: The number of remaining bacteria is 0 (total annihilation).
The results are shown in Table 1.
実施例１−２
歯周病患者１０人に対して１２５０ｐｐｍのエチレンジアミン四酢酸（ＥＤＴＡ）銅キレート錯体水溶液にて、朝夕２回、洗口して２週間後の経過を診た。Example 1-2
Ten patients with periodontal disease were rinsed twice a day in the morning and evening with a 1250 ppm ethylenediaminetetraacetic acid (EDTA) copper chelate complex aqueous solution, and the course after 2 weeks was examined.
結果、すべての患者で改善がみられた。 As a result, all patients showed improvement.
実施例２
＜Ｎ−（２−ヒドロキシエチル）エチレンジアミン−Ｎ，Ｎ’，Ｎ’−三酢酸（ＨＥＤＴＡ）銅キレート錯体水溶液作成＞
Ｎ−（２−ヒドロキシエチル）エチレンジアミン−Ｎ，Ｎ’，Ｎ’−三酢酸三ナトリウム二水和物（東京化成工業株式会社製）８．１６ｇをイオン交換水にて１Ｌに溶解する。該溶液を有限会社エルアンドアール製の銅イオン水生成器「銅しましょ」にて７時間通電して、２４時間放置後、ろ過し、１５００ｐｐｍの銅−ＨＥＤＴＡキレート水溶液を１Ｌ作成。Example 2
<N- (2-hydroxyethyl) ethylenediamine-N, N ', N'-triacetic acid (HEDTA) copper chelate complex aqueous solution preparation>
8.16 g of N- (2-hydroxyethyl) ethylenediamine-N, N ′, N′-triacetic acid trisodium dihydrate (manufactured by Tokyo Chemical Industry Co., Ltd.) is dissolved in 1 L with ion-exchanged water. The solution was energized for 7 hours in a copper ion water generator “Copper Shimasho” manufactured by L & R Co., Ltd., allowed to stand for 24 hours, and then filtered to prepare 1 L of a 1500 ppm copper-HEDTA chelate aqueous solution.
上記１５００ｐｐｍの銅−ＨＥＤＴＡキレート水溶液を用いて下記の濃度に調整し作成する。
銅濃度として、
（Ａ−２）３００ｐｐｍは、
該銅−ＨＥＤＴＡキレート水溶液を５倍に希釈し１００ｍｌとする溶液。
（Ｂ−２）５００ｐｐｍは、
該銅−ＨＥＤＴＡキレート水溶液を３倍に希釈し１００ｍｌとする溶液。
（Ｃ−２）７５０ｐｐｍは、
該銅−ＨＥＤＴＡキレート水溶液を２倍に希釈し１００ｍｌとする溶液。
（Ｄ−２）１０００ｐｐｍは、
該銅−ＨＥＤＴＡキレート水溶液を１．５倍に希釈し１００ｍｌとする溶液。
（Ｅ−２）１２５０ｐｐｍは、
該銅−ＨＥＤＴＡキレート水溶液を１．２倍に希釈し１００ｍｌとする溶液。
（Ｆ−２）１５００ｐｐｍは、
該銅−ＨＥＤＴＡキレート水溶液を１００ｍｌとする溶液。
をそれぞれ作成した。Using the 1500 ppm copper-HEDTA chelate aqueous solution, the concentration is adjusted to the following concentration.
As copper concentration,
(A-2) 300 ppm is
A solution obtained by diluting the copper-HEDTA chelate aqueous solution 5 times to 100 ml.
(B-2) 500 ppm is
A solution obtained by diluting the copper-HEDTA chelate aqueous solution 3 times to 100 ml.
(C-2) 750 ppm is
A solution obtained by diluting the copper-HEDTA chelate aqueous solution twice to 100 ml.
(D-2) 1000 ppm is
A solution obtained by diluting the copper-HEDTA chelate aqueous solution 1.5 times to 100 ml.
(E-2) 1250 ppm is
A solution obtained by diluting the copper-HEDTA chelate aqueous solution 1.2 times to 100 ml.
(F-2) 1500 ppm is
The solution which makes this copper-HEDTA chelate aqueous solution 100 ml.
Was created respectively.
＜ｐＨ３．０の希塩酸作成＞
ｐＨメーターで測定しながら、１００ｍＬのイオン交換水に１Ｎの塩酸をパスツールピペットで１滴ずつ入れていきｐＨ３．０の塩酸を作成する。<Preparation of dilute hydrochloric acid with pH 3.0>
While measuring with a pH meter, 1N hydrochloric acid is added dropwise to 100 mL of ion exchange water with a Pasteur pipette to prepare hydrochloric acid having a pH of 3.0.
大腸菌は、酸に対して非常に耐性が高い、そのため酸性下の殺菌力評価に大腸菌を用いた。 Escherichia coli is very resistant to acids, and therefore E. coli was used for evaluation of bactericidal activity under acidic conditions.
「殺菌力評価」
殺菌・抗菌用組成物が、銅濃度といて、比較例は０質量％、上記で調整した（Ａ−２）、（Ｂ−２）、（Ｃ−２）、（Ｄ−２）、（Ｅ−２）、（Ｆ−２）の溶液から試験液として８．９ｍＬをそれぞれ取り、ｐＨ３．０の希塩酸１ｍＬを各試験液に加え、さらに各試験液へ菌数が１００個／ｍＬとなるように調整された大腸菌母液（ＩＦＯ３９７２）０．１ｍＬを添加し、均一に攪拌した。１０分後に１ｍＬ採取し、９ｍＬのＳＣＤＬＰ培地（Ｓｏｙｂｅａｎ−Ｃａｓｅｉｎ Ｄｉｇｅｓｔ Ｂｒｏｔｈ ｗｉｔｈ Ｌｅｃｔｉｎ ＆ Ｐｏｌｙｓｏｒｂａｔｅ ８０：和光純薬工業株式会社製）に加え、１０倍希釈液とした。得られた希釈液をさらに１０倍に希釈する操作を４回繰り返し、１０倍から１０００００倍の希釈を得た。これら各希釈液から１．０ｍＬをシャーレに採取し、ＳＣＤＬＰ寒天培地（Ｓｏｙｂｅａｎ−Ｃａｓｅｉｎ Ｄｉｇｅｓｔ Ａｇｅｒ ｗｉｔｈ Ｌｅｃｔｉｎ ＆ Ｐｏｌｙｓｏｒｂａｔｅ ８０：和光純薬工業株式会社製）１５ｍＬを加えて均一化し、３７℃で２日間培養した後、コロニー数７０〜３００の範囲にあるものを選んでコロニーをカウントして生存菌数を求め、初菌数の対数値と試験後の生存菌数の対数値との差を殺菌数とした。"Bactericidal evaluation"
The composition for sterilization / antibacterial is copper concentration, and the comparative example is 0% by mass, adjusted as described above (A-2), (B-2), (C-2), (D-2), (E -2) Take 8.9 mL of the test solution from the solution of (F-2), add 1 mL of dilute hydrochloric acid of pH 3.0 to each test solution, and further increase the number of bacteria to 100 / mL in each test solution. 0.1 mL of the Escherichia coli mother liquor (IFO3972) prepared in the above was added and stirred uniformly. After 10 minutes, 1 mL was collected and added to 9 mL of SCDLP medium (Soybean-Casein Digest Broth With Lectin & Polysorbate 80: manufactured by Wako Pure Chemical Industries, Ltd.) to give a 10-fold dilution. The operation of further diluting the obtained diluted solution 10 times was repeated 4 times to obtain 10 times to 100,000 times dilution. Collect 1.0 mL from each of these dilutions in a petri dish, add 15 mL of SCDLP agar medium (Soybean-Casein Digest Age with Lectin & Polysorbate 80: Wako Pure Chemical Industries, Ltd.), homogenize, and culture at 37 ° C. for 2 days After that, the number of colonies in the range of 70-300 is selected and the number of colonies is counted to determine the number of surviving bacteria. did.
（殺菌力評価基準）
比較例の場合と比較して、以下の４段階で殺菌力を評価した。
・大腸菌に対する抗菌効果基準
×：殺菌数１桁未満。
△：殺菌数２桁未満。
○：殺菌数２桁以上だが、全滅には至らない。
◎：残存菌数０（全滅）。
結果を表２に示す。(Sterilization power evaluation criteria)
Compared to the comparative example, the sterilizing power was evaluated in the following four stages.
-Antibacterial effect standard against E. coli ×: Number of sterilizations is less than one digit.
Δ: The number of sterilizations is less than 2 digits.
○: The number of sterilization is 2 digits or more, but it is not annihilated.
A: The number of remaining bacteria is 0 (total annihilation).
The results are shown in Table 2.
実施例２−２
歯周病患者１０人に対して１２５０ｐｐｍのＮ−（２−ヒドロキシエチル）エチレンジアミン−Ｎ，Ｎ’，Ｎ’−三酢酸（ＨＥＤＴＡ）銅キレート錯体水溶液にて、朝夕２回、洗口して２週間後の経過を診た。Example 2-2
Wash 2 times in the morning and evening with 1250 ppm N- (2-hydroxyethyl) ethylenediamine-N, N ′, N′-triacetic acid (HEDTA) copper chelate complex aqueous solution for 10 patients with periodontal disease. We examined the progress after a week.
結果、すべての患者で改善がみられた。 As a result, all patients showed improvement.
本発明によれば、エチレンジアミン四酢酸（ＥＤＴＡ）銅キレート錯体、Ｎ−（２−ヒドロキシエチル）エチレンジアミン−Ｎ，Ｎ’，Ｎ’−三酢酸（ＨＥＤＴＡ）銅キレート錯体が、人体に対して抗生物質を用いることなく殺菌・抗菌することができ、そのため耐性菌を増やすことがなく、副作用が少なくない殺菌・抗菌組成物を提供することができる。 According to the present invention, an ethylenediaminetetraacetic acid (EDTA) copper chelate complex, an N- (2-hydroxyethyl) ethylenediamine-N, N ′, N′-triacetic acid (HEDTA) copper chelate complex is an antibiotic against the human body. Therefore, it is possible to provide a bactericidal / antibacterial composition that does not increase the number of resistant bacteria and has few side effects.
Claims (2)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2017166172A JP2019034921A (en) | 2017-08-15 | 2017-08-15 | Bactericidal and antibacterial composition |
| JP2021210632A JP7217054B2 (en) | 2017-08-15 | 2021-12-24 | Sterilizing/antibacterial composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2017166172A JP2019034921A (en) | 2017-08-15 | 2017-08-15 | Bactericidal and antibacterial composition |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021210632A Division JP7217054B2 (en) | 2017-08-15 | 2021-12-24 | Sterilizing/antibacterial composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2019034921A true JP2019034921A (en) | 2019-03-07 |
| JP2019034921A5 JP2019034921A5 (en) | 2019-10-17 |
Family
ID=65636909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017166172A Pending JP2019034921A (en) | 2017-08-15 | 2017-08-15 | Bactericidal and antibacterial composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2019034921A (en) |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996003881A1 (en) * | 1994-07-29 | 1996-02-15 | Toto Ltd. | Strongly acidic sterile water containing low-concentration hypochlorous acid, method of forming strongly acidic sterile water containing low-concentration hypochlorous acid, apparatus therefor, and apparatus for forming and delivering strongly acidic sterile water containing low-concentration hypochlorous acid |
| JP2000247893A (en) * | 1999-03-01 | 2000-09-12 | Kansai Koso Kk | Antimicrobial agent, bathing agent composition and skin cleansing agent composition |
| JP2004051635A (en) * | 2002-07-18 | 2004-02-19 | Rohm & Haas Co | Stabilized haloalkynyl microbicide composition |
| JP2005510328A (en) * | 2001-12-05 | 2005-04-21 | アセプティカ インコーポレイテッド | Antimicrobial system and method |
| JP2005314336A (en) * | 2004-04-30 | 2005-11-10 | Nof Corp | Composition for disinfecting skin and method for mitigating skin irritation |
| JP2006526664A (en) * | 2003-06-04 | 2006-11-24 | タイコ・ヘルスケアー・グループ・エルピー | Bactericidal composition, method and system |
| JP2013170160A (en) * | 2012-02-22 | 2013-09-02 | Adeka Corp | Peptide-containing antimicrobial composition |
| JP2014500229A (en) * | 2010-08-20 | 2014-01-09 | ダウ アグロサイエンシィズ エルエルシー | Synergistic fungicidal and algicidal composition comprising 7-hydroxy-indanone benzoylhydrazone and copper |
| JP2014193849A (en) * | 2013-02-27 | 2014-10-09 | Asahikawa Medical College | Method for enhancing bactericidal action of porphyrin derivatives |
| WO2017079589A1 (en) * | 2015-11-05 | 2017-05-11 | Board Of Regents, The University Of Texas System | Antimicrobial solutions with enhanced stability |
-
2017
- 2017-08-15 JP JP2017166172A patent/JP2019034921A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996003881A1 (en) * | 1994-07-29 | 1996-02-15 | Toto Ltd. | Strongly acidic sterile water containing low-concentration hypochlorous acid, method of forming strongly acidic sterile water containing low-concentration hypochlorous acid, apparatus therefor, and apparatus for forming and delivering strongly acidic sterile water containing low-concentration hypochlorous acid |
| JP2000247893A (en) * | 1999-03-01 | 2000-09-12 | Kansai Koso Kk | Antimicrobial agent, bathing agent composition and skin cleansing agent composition |
| JP2005510328A (en) * | 2001-12-05 | 2005-04-21 | アセプティカ インコーポレイテッド | Antimicrobial system and method |
| JP2004051635A (en) * | 2002-07-18 | 2004-02-19 | Rohm & Haas Co | Stabilized haloalkynyl microbicide composition |
| JP2006526664A (en) * | 2003-06-04 | 2006-11-24 | タイコ・ヘルスケアー・グループ・エルピー | Bactericidal composition, method and system |
| JP2005314336A (en) * | 2004-04-30 | 2005-11-10 | Nof Corp | Composition for disinfecting skin and method for mitigating skin irritation |
| JP2014500229A (en) * | 2010-08-20 | 2014-01-09 | ダウ アグロサイエンシィズ エルエルシー | Synergistic fungicidal and algicidal composition comprising 7-hydroxy-indanone benzoylhydrazone and copper |
| JP2013170160A (en) * | 2012-02-22 | 2013-09-02 | Adeka Corp | Peptide-containing antimicrobial composition |
| JP2014193849A (en) * | 2013-02-27 | 2014-10-09 | Asahikawa Medical College | Method for enhancing bactericidal action of porphyrin derivatives |
| WO2017079589A1 (en) * | 2015-11-05 | 2017-05-11 | Board Of Regents, The University Of Texas System | Antimicrobial solutions with enhanced stability |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4258056A (en) | Control of mastitis and compositions therefor | |
| EP1765081B1 (en) | Hydrogen peroxide-based skin disinfectant | |
| JPS61112002A (en) | Method of decreasing corrosion with aqueous disinfectant solution | |
| CN104306176B (en) | A kind of quaternary anti-bacterial hand sanitizer | |
| JP2017512824A (en) | Quick-acting disinfectant composition | |
| AR074541A1 (en) | NATURAL SILVER DISINFECTANT COMPOSITIONS | |
| EP4129067A1 (en) | Composite quaternary ammonium salt disinfectant and preparation method therefor | |
| CN111838174A (en) | A kind of hydrogen peroxide disinfectant and preparation method thereof | |
| WO2023275536A1 (en) | Laundry sanitizing composition | |
| JP2013534921A (en) | Disinfecting and disinfecting liquid | |
| DE1642056A1 (en) | Antimicrobial agents | |
| CA2900493C (en) | Composition and method for eliminating spores | |
| JP7217054B2 (en) | Sterilizing/antibacterial composition | |
| JP2019034921A (en) | Bactericidal and antibacterial composition | |
| JP2842715B2 (en) | Disinfectant cleaning composition | |
| US20240400947A1 (en) | Triamine-Based Disinfecting Cleaning Composition | |
| JPH02115105A (en) | Sterilizing and disinfecting agent composition | |
| CN104523667A (en) | Combination technology for composite quaternary ammonium salt skin mucosa disinfectant | |
| US20240032535A1 (en) | Antimicrobial compositions and methods with supramolecular structures | |
| EP4112706A1 (en) | Laundry sanitizing composition | |
| JP5601793B2 (en) | Biofilm remover composition | |
| EA025997B1 (en) | Composition for producing a disinfectant having a washing effect | |
| JPH032841B2 (en) | ||
| JP2009249499A (en) | Antibacterial detergent for dialysis equipment | |
| RU2525435C1 (en) | Tableted antimicrobial composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190807 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200518 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20200518 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20200518 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210512 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210706 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20210929 |