WO2021248674A1 - 一种抗菌纳米酶及其制备方法 - Google Patents
一种抗菌纳米酶及其制备方法 Download PDFInfo
- Publication number
- WO2021248674A1 WO2021248674A1 PCT/CN2020/108169 CN2020108169W WO2021248674A1 WO 2021248674 A1 WO2021248674 A1 WO 2021248674A1 CN 2020108169 W CN2020108169 W CN 2020108169W WO 2021248674 A1 WO2021248674 A1 WO 2021248674A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- solution
- antibacterial
- aqueous solution
- preparation
- nanoenzyme
- Prior art date
Links
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 229910021389 graphene Inorganic materials 0.000 claims abstract description 44
- 239000002253 acid Substances 0.000 claims abstract description 36
- WTDHULULXKLSOZ-UHFFFAOYSA-N hydroxylamine hydrochloride Substances Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims abstract description 35
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000010931 gold Substances 0.000 claims abstract description 23
- 229910052737 gold Inorganic materials 0.000 claims abstract description 23
- 238000003756 stirring Methods 0.000 claims abstract description 23
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims abstract description 22
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims abstract description 17
- 239000001509 sodium citrate Substances 0.000 claims abstract description 17
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 claims abstract description 14
- 229940025294 hemin Drugs 0.000 claims abstract description 14
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims abstract description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims abstract description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 11
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000005119 centrifugation Methods 0.000 claims abstract description 4
- 239000007864 aqueous solution Substances 0.000 claims description 53
- 239000000243 solution Substances 0.000 claims description 42
- 238000002604 ultrasonography Methods 0.000 claims description 13
- 241000894006 Bacteria Species 0.000 claims description 9
- 241000588724 Escherichia coli Species 0.000 claims description 9
- 239000002131 composite material Substances 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 4
- 239000001301 oxygen Substances 0.000 abstract description 4
- 238000004140 cleaning Methods 0.000 abstract description 3
- 238000001816 cooling Methods 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract description 3
- 238000009835 boiling Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 238000002156 mixing Methods 0.000 abstract 2
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 abstract 1
- 230000001580 bacterial effect Effects 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000010586 diagram Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002057 nanoflower Substances 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/242—Gold; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/10—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
- B22F1/05—Metallic powder characterised by the size or surface area of the particles
- B22F1/054—Nanosized particles
- B22F1/0553—Complex form nanoparticles, e.g. prism, pyramid, octahedron
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
- B22F1/07—Metallic powder characterised by particles having a nanoscale microstructure
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F9/00—Making metallic powder or suspensions thereof
- B22F9/16—Making metallic powder or suspensions thereof using chemical processes
- B22F9/18—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds
- B22F9/24—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds starting from liquid metal compounds, e.g. solutions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
- C01B32/182—Graphene
- C01B32/184—Preparation
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
- C01B32/182—Graphene
- C01B32/194—After-treatment
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
- C01B32/182—Graphene
- C01B32/198—Graphene oxide
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
Definitions
- the ratio of the volume of the aqueous ammonia solution, the mass of hemin, the volume of hydrazine hydrate, and the volume of the graphene oxide aqueous solution after ultrasound is preferably 60 ⁇ L: 10 mg: 10 ⁇ L: 40 mL.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nanotechnology (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials Engineering (AREA)
- Crystallography & Structural Chemistry (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- Composite Materials (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Manufacturing & Machinery (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
一种抗菌纳米酶及其制备方法,属于抗菌材料技术领域。制备方法如下:1)对氯金酸水溶液进行加热和搅拌,加入柠檬酸钠水溶液,煮沸,冷却得到金种溶液;2)将氨水溶液、氯化血红素、水合肼和超声后的氧化石墨烯水溶液混合,加热反应,离心,清洗,烘干,得到hemin-石墨烯复合物;3)将盐酸羟胺水溶液、步骤1)得到的金种溶液、步骤2)得到的hemin-石墨烯复合物和氯金酸水溶液混合,搅拌至溶液变为蓝绿色,再搅拌后,停止搅拌,静置,得到纳米酶。所述纳米酶在808nm近红外激光照射下产生的光热性能,以及纳米酶表面产生的活性氧自由基使其能够高效抗菌。
Description
本申请要求于2020年06月11日提交中国专利局、申请号为CN202010529936.9、发明名称为“一种抗菌纳米酶及其制备方法”的中国专利申请的优先权,其全部内容通过引用结合在本申请中。
本发明涉及抗菌材料技术领域,具体涉及一种抗菌纳米酶及其制备方法。
细菌污染是最常见的食品、环境污染之一,受细菌污染的食品会导致多种疾病。目前常用的灭菌消毒剂包括氧化剂、重金属盐、有机化合物等。化学类疗剂包括抗代谢药物或者抗生素能作用于病原微生物新陈代谢的某个环节,使其生长受到抑制或致死。但是长期使用容易使细菌产生抗药性,严重影响后期灭菌效果。
发明内容
本发明的目的在于提供一种抗菌纳米酶及其制备方法。本发明所述纳米酶在808nm近红外激光照射下产生的光热性能,以及纳米酶表面产生的活性氧自由基使其能够高效抗菌。
本发明提供了一种抗菌纳米酶的制备方法,包括以下步骤:
1)对氯金酸水溶液进行加热和搅拌,加入柠檬酸钠水溶液,煮沸20~30min,冷却得到金种溶液;
2)将氨水溶液、氯化血红素、水合肼和超声后的氧化石墨烯水溶液混合,加热至60~70℃反应3~4h,离心,清洗,烘干,得到hemin-石墨烯复合物;
3)将盐酸羟胺水溶液、步骤1)得到的金种溶液、步骤2)得到的hemin-石墨烯复合物和pH值为11~12的氯金酸水溶液混合,搅拌至溶液变为蓝绿色,再搅拌3~5min后,停止搅拌,静置8~12h,得到纳米酶;
所述步骤1)和步骤2)没有时间先后顺序的限定。
优选的是,步骤1)中,所述氯金酸水溶液中氯金酸的质量百分浓度为0.01%~0.02%,所述柠檬酸钠水溶液中柠檬酸钠的质量百分浓度为1%~2%,所述氯金酸水溶液和所述柠檬酸钠水溶液的体积比为50:(0.75~1.5)。
优选的是,步骤2)所述氧化石墨烯水溶液中氧化石墨烯的质量浓度为0.2~0.5mg/mL。
优选的是,步骤2)所述超声后,氧化石墨烯的粒径为200nm~1μm。
优选的是,步骤2)中,所述氨水溶液的体积、氯化血红素的质量、水合肼的体积和超声后氧化石墨烯水溶液的体积比优选为60μL:10mg:10μL:40mL。
优选的是,步骤2)所述离心的条件为11000rpm,30min。
优选的是,步骤3)中,所述盐酸羟胺水溶液的体积、金种溶液的体积、hemin-石墨烯复合物的质量和pH值为11~12的氯金酸水溶液的体积比为300μL:12mL:0.02g:20mL;所述盐酸羟胺水溶液中盐酸羟胺的摩尔浓度为0.02M;所述氯金酸水溶液中氯金酸的质量百分浓度为0.01%。
本发明还提供了利用上述技术方案所述制备方法得到的抗菌纳米酶。
本发明还提供了利用上述技术方案所述制备方法得到的抗菌纳米酶或上述技术方案所述抗菌纳米酶在抗菌中的应用。
优选的是,所述应用中,向所述抗菌纳米酶提供808nm的近红外激光照射。
本发明提供了一种抗菌纳米酶的制备方法。本发明所述制备方法通过在还原后的氧化石墨烯表面原位还原氯金酸溶液,合成基于石墨烯和花型金纳米花的抗菌纳米酶复合物。本发明制备方法合成的纳米酶在808nm激光照射下迅速升温,同时产生活性氧,能产生较好的抗菌效果。较传统的化学类抗菌试剂,对环境无毒副作用,且保持优良抗菌效果的同时避免了细菌抗药性的产生。
说明书附图
图1为本发明提供的纳米酶的透射电镜表征图;
图2为本发明提供的纳米酶的抗菌效果图。
本发明提供了一种抗菌纳米酶的制备方法,包括以下步骤:
1)对氯金酸水溶液进行加热和搅拌,加入柠檬酸钠水溶液,煮沸20~30min,冷却得到金种溶液;
2)将氨水溶液、氯化血红素、水合肼和超声后的氧化石墨烯水溶液混合,加热至60~70℃反应3~4h,离心,清洗,烘干,得到hemin-石墨烯复合物;
3)将盐酸羟胺水溶液、步骤1)得到的金种溶液、步骤2)得到的hemin-石墨烯复合物和pH值为11~12的氯金酸水溶液混合,搅拌至溶液变为蓝绿色3~5min后,停止搅拌,静置8~12h,得到纳米酶;
所述步骤1)和步骤2)没有时间先后顺序的限定。
本发明对氯金酸水溶液进行加热和搅拌,加入柠檬酸钠水溶液,煮沸20~30min,冷却得到金种溶液。在本发明中,所述氯金酸水溶液中氯金酸的质量百分浓度优选为0.01%~0.02%,所述柠檬酸钠水溶液中柠檬酸钠的质量百分浓度优选为1%~2%,所述氯金酸水溶液和所述柠檬酸钠水溶液的体积比优选为50:(0.75~1.5)。更具体的,本发明优选配制50mL质量百分浓度为0.01%的氯金酸溶液,加热并搅拌,快速加入750μL质量百分浓度为1%的柠檬酸钠水溶液。本发明优选进行自然冷却,优选冷却至室温。本发明得到的金种溶液优选存放于4℃冰箱待用。本发明对所述氯金酸和柠檬酸钠的来源没有特殊限定,采用本领域技术人员熟知的氯金酸和柠檬酸钠的常规市售产品即可。
本发明将氨水溶液、氯化血红素、水合肼和超声后的氧化石墨烯水溶液混合,加热至60~70℃反应3~4h,更优选60℃反应4h,离心,清洗,烘干,得到hemin-石墨烯复合物。本发明对所述氧化石墨烯的来源没有特殊限定,优选为购自南京先丰纳米材料科技有限公司,浓度为2mg/mL的氧化石墨烯分散液。本发明优选取5mL氧化石墨烯分散液,加入35mL水中,超声得到超声后的氧化石墨烯水溶液。在本发明中,所述超声的时间优选为30min。在本发明中,所述超声后,氧化石墨烯的粒径优选为 200nm~1μm,更优选为500nm。在本发明中,所述氧化石墨烯水溶液中氧化石墨烯的质量浓度优选为0.2~0.5mg/mL,更优选为0.25mg/mL。在本发明中,所述氨水溶液的体积、氯化血红素的质量、水合肼的体积和超声后氧化石墨烯水溶液的体积比优选为60μL:10mg:10μL:40mL。具体的,本发明优选在40mL超声后的氧化石墨烯水溶液中加入60μL氨水溶液,10mg氯化血红素和10μL水合肼。本发明中,所述离心的条件优选为11000rpm,30min。本发明对所述氨水溶液、氯化血红素和水合肼的来源没有特殊限定,采用本领域技术人员熟知的常规市售产品即可,所述氯化血红素优选购自西格玛有限公司。本发明所述清洗优选使用超纯水进行,所述清洗的次数优选为2次。
得到金种溶液和hemin-石墨烯复合物后,本发明将盐酸羟胺水溶液、金种溶液、hemin-石墨烯复合物和pH值为11~12的氯金酸水溶液混合,搅拌至溶液变为蓝绿色,再搅拌3~5min后,停止搅拌,静置8~12h,得到纳米酶。本发明在氧化石墨烯表面原位合成花型金纳米颗粒,构建纳米酶复合物。在本发明中,所述盐酸羟胺水溶液的体积、金种溶液的体积、hemin-石墨烯复合物的质量和pH值为11~12的氯金酸水溶液的体积比优选为300μL:12mL:0.02g:20mL;所述盐酸羟胺水溶液中盐酸羟胺的摩尔浓度为0.02M;所述氯金酸水溶液中氯金酸的质量百分浓度为0.01%。在本发明中,所述氯金酸水溶液的pH值更优选为11.5。具体的,本发明优选将50mL氯金酸水溶液(质量百分浓度为0.01%)用浓度为1M的氢氧化钠调整pH为11.5,加入12mL金种溶液,300μL 0.02M盐酸羟胺,和0.02g hemin-石墨烯复合物。本发明对盐酸羟胺的来源没有特殊限定,采用本领域技术人员熟知的常规盐酸羟胺市售产品即可。
本发明还提供了上述技术方案所述制备方法得到的抗菌纳米酶。本发明所述纳米酶在808nm激光照射下迅速升温,同时产生活性氧,产生较好的抗菌效果。即本发明利用所述纳米酶的强光热性能和催化性质,实现高效、安全的抗菌效果。
本发明还提供了上述技术方案所述制备方法得到的抗菌纳米酶或上 述技术方案所述抗菌纳米酶在抗菌中的应用。例如用于耐药大肠杆菌的杀菌抗菌处理。
本发明所述应用中,优选需要向所述抗菌纳米酶提供808nm的近红外激光照射。
下面结合具体实施例对本发明所述的一种抗菌纳米酶及其制备方法做进一步详细的介绍,本发明的技术方案包括但不限于以下实施例。
实施例1
纳米酶的制备方法
首先合成金种溶液,将所有玻璃容器清洗干净烘干。配制50mL质量百分浓度为0.01%氯金酸水溶液,将溶液加热并搅拌,快速加入750μL质量百分浓度为1%的柠檬酸钠水溶液,保持煮沸状态20min后停止加热,自然冷却至室温,存放于4℃冰箱待用。
合成hemin-石墨烯复合物,35mL水中加入5mL氧化石墨烯分散液,超声30min。加入60μL氨水溶液,10mg氯化血红素和10μL水合肼,在60℃条件下保持4h。随后,离心该溶液(11000rpm,30min),期间用超纯水清洗2次。制得的溶液烘干存放于4℃冰箱待用。
最后合成hemin-石墨烯-金纳米花复合物,50mL氯金酸(0.01%)用浓度为1M的氢氧化钠调整pH为11.5,加入12mL制备的金种溶液,300μL0.02M盐酸羟胺,以及0.02g制备的hemin-石墨烯复合物,并不断搅拌。溶液颜色变为蓝绿色。3min后停止搅拌过夜,制得纳米酶溶液,如图1所示(合成的纳米酶的透射电镜表征图,从电镜图中可以看出石墨烯表面原位生长了很花型金纳米颗粒(粒径在50nm左右),粒径比较均一)。
实施例2
纳米酶在激光照射下对耐药大肠杆菌(Ampr E.coli)的抗菌性能
100μg/mL纳米酶溶液和1.0×10
5CFU mL
-1细菌共同孵育20min,稀释100倍后取100μL细菌悬浊液平铺到培养皿中的LB培养基上,37C孵育18h。开启808nm的激光器,电流调至0.5A,将培养皿放置激光探头下照射10min后记录细菌存活率,同时使用不含纳米酶溶液的细菌培养皿(细菌浓度为1.0×10
5CFU mL
-1)作为对照组,采用相同的实验操 作。
其实验结果:808nm激光照射10min后,不含纳米酶溶液的细菌培养皿的细菌存活率为99%,含有100μg.mL
-1纳米酶溶液的细菌培养皿中细菌存活率为28%。表明纳米酶对耐药大肠杆菌(Ampr E.coli)具有很好的杀菌效果,如图2(纳米酶的抗菌效果图)所示,其中,A为不含纳米酶溶液的细菌培养皿经808nm激光照射10min后图片;B为含100ug.ml
-1纳米酶溶液的细菌培养皿经808nm激光照射10min后图片。
实施例3
不同浓度纳米酶激光照射下对耐药大肠杆菌(Ampr E.coli)的抗菌性能
实验分为5组,分别将浓度为0μg/mL(组1),50μg/mL(组2),80μg/mL(组3),100μg/mL(组4),120μg/mL(组5)的纳米酶溶液和1.0×105CFU mL-1细菌共同孵育20min,稀释100倍后取100μL细菌悬浊液平铺到培养皿中的LB培养基上,37℃孵育18h。开启808nm的激光器,电流调至0.5A,将培养皿放置激光探头下照射10min后记录细菌存活率,组1细菌存活率为97.5%,组2细菌存活率为76.2%,组3细菌存活率为55.2%,组4细菌存活率为28.6%,组5细菌存活率为18.8%。表明纳米酶对耐药大肠杆菌(Ampr E.coli)的杀菌效果与纳米酶浓度相关,在一定范围内纳米酶浓度越大,杀菌效果越好.
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (15)
- 一种抗菌纳米酶的制备方法,包括以下步骤:1)对氯金酸水溶液进行加热和搅拌,加入柠檬酸钠水溶液,煮沸20~30min,冷却得到金种溶液;2)将氨水溶液、氯化血红素、水合肼和超声后的氧化石墨烯水溶液混合,加热至60~70℃反应3~4h,离心,清洗,烘干,得到hemin-石墨烯复合物;3)将盐酸羟胺水溶液、步骤1)得到的金种溶液、步骤2)得到的hemin-石墨烯复合物和pH值为11~12的氯金酸水溶液混合,搅拌至溶液变为蓝绿色,再搅拌3~5min后,停止搅拌,静置8~12h,得到纳米酶;所述步骤1)和步骤2)没有时间先后顺序的限定。
- 根据权利要求1所述的制备方法,其特征在于,步骤1)中,所述氯金酸水溶液中氯金酸的质量百分浓度为0.01%~0.02%,所述柠檬酸钠水溶液中柠檬酸钠的质量百分浓度为1%~2%,所述氯金酸水溶液和所述柠檬酸钠水溶液的体积比为50:(0.75~1.5)。
- 根据权利要求1所述的制备方法,其特征在于,步骤2)所述氧化石墨烯水溶液中氧化石墨烯的质量浓度为0.2~0.5mg/mL。
- 根据权利要求1所述的制备方法,其特征在于,步骤2)所述超声后,氧化石墨烯的粒径为200nm~1μm。
- 根据权利要求1所述的制备方法,其特征在于,步骤2)中,所述氨水溶液的体积、氯化血红素的质量、水合肼的体积和超声后氧化石墨烯水溶液的体积比优选为60μL:10mg:10μL:40mL。
- 根据权利要求1所述的制备方法,其特征在于,步骤2)所述离心的条件为11000rpm,30min。
- 根据权利要求1所述的制备方法,其特征在于,步骤3)中,所述盐酸羟胺水溶液的体积、金种溶液的体积、hemin-石墨烯复合物的质量和pH值为11~12的氯金酸水溶液的体积比为300μL:12mL:0.02g:20mL; 所述盐酸羟胺水溶液中盐酸羟胺的摩尔浓度为0.02M;所述氯金酸水溶液中氯金酸的质量百分浓度为0.01%。
- 利用权利要求1~7任一项所述制备方法得到的抗菌纳米酶。
- 利用权利要求1~7任一项所述制备方法得到的抗菌纳米酶或权利要求8所述抗菌纳米酶在抗菌中的应用。
- 根据权利要求9所述的应用,其特征在于,所述应用中,向所述抗菌纳米酶提供808nm的近红外激光照射。
- 利用权利要求1~7任一项所述制备方法得到的抗菌纳米酶或权利要求8所述抗菌纳米酶在抗耐药细菌中的应用。
- 根据权利要求11所述的应用,其特征在于,所述应用中,向所述抗菌纳米酶提供808nm的近红外激光照射。
- 根据权利要求11所述的应用,其特征在于,所述耐药细菌包括耐药大肠杆菌。
- 权利要求1~7任一项所述制备方法得到的抗菌纳米酶或权利要求8所述抗菌纳米酶治疗细菌感染疾病的方法。
- 根据权利要求14所述的方法,其特征在于,向所述抗菌纳米酶提供808nm的近红外激光照射。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010529936.9A CN111632141A (zh) | 2020-06-11 | 2020-06-11 | 一种抗菌纳米酶及其制备方法 |
CN202010529936.9 | 2020-06-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021248674A1 true WO2021248674A1 (zh) | 2021-12-16 |
Family
ID=72322929
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2020/108169 WO2021248674A1 (zh) | 2020-06-11 | 2020-08-10 | 一种抗菌纳米酶及其制备方法 |
Country Status (3)
Country | Link |
---|---|
CN (1) | CN111632141A (zh) |
NL (1) | NL2028410B1 (zh) |
WO (1) | WO2021248674A1 (zh) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114010619A (zh) * | 2021-11-30 | 2022-02-08 | 江南大学 | 一种功能性纳米平台的构建及应用 |
CN114505070A (zh) * | 2022-04-02 | 2022-05-17 | 陕西师范大学 | 多孔纳米酶、多孔纳米酶晶体及其制备方法和应用 |
CN114669312A (zh) * | 2022-02-23 | 2022-06-28 | 东南大学 | 一种整合酶的制备方法 |
CN114713261A (zh) * | 2022-04-08 | 2022-07-08 | 国科温州研究院(温州生物材料与工程研究所) | 一种多功能纳米酶、制备方法及其应用 |
CN115121259A (zh) * | 2022-05-10 | 2022-09-30 | 陕西师范大学 | 氧化亚铜@金纳米模拟酶及制备方法和应用 |
CN115121277A (zh) * | 2022-07-05 | 2022-09-30 | 合肥工业大学 | 一种碘掺杂单原子纳米酶CoCNI及其制备方法和应用 |
CN115646486A (zh) * | 2022-11-10 | 2023-01-31 | 辽宁大学 | 一种石墨烯负载钯纳米酶及其制备方法和应用 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112402632B (zh) * | 2020-11-24 | 2022-01-07 | 南京大学 | 一种放疗增敏用纳米级配位聚合物及其制备方法和用途 |
CN116082663A (zh) * | 2021-11-05 | 2023-05-09 | 温州医科大学 | 一种光动力抗菌水凝胶及其制备方法和应用 |
CN114053473B (zh) * | 2021-11-10 | 2022-10-18 | 昆明理工大学 | 一种四氧化三铁复合纳米酶抗菌剂的制备方法及应用 |
CN114452386B (zh) * | 2022-01-14 | 2023-10-10 | 江苏大学 | 金铜双金属纳米酶复合材料的制备方法和应用 |
CN115709099B (zh) * | 2022-10-28 | 2024-01-26 | 湖南大学 | 负载单原子纳米酶Fe-N-C的聚偏氟乙烯复合膜及其制备方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103551194A (zh) * | 2013-11-14 | 2014-02-05 | 厦门大学 | 石墨烯-血红素及纳米金三元复合材料及制备方法与应用 |
CN104597240A (zh) * | 2015-02-02 | 2015-05-06 | 广西医科大学 | 石墨烯/类过氧化物酶双信号放大检测白血病的生物传感方法 |
CN107314981A (zh) * | 2017-07-31 | 2017-11-03 | 河南大学 | 基于hemin‑石墨烯复合材料分析检测PARP活性的方法 |
CN111505077A (zh) * | 2020-04-26 | 2020-08-07 | 桂林电子科技大学 | 一种基于RGO-Hemin/Au NPs纳米复合材料检测GPC3的方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107127351B (zh) * | 2017-05-03 | 2019-03-19 | 广州特种承压设备检测研究院 | 石墨烯与四氧化三铁@金复合材料及其制备方法和应用 |
CN107598185B (zh) * | 2017-08-29 | 2020-07-28 | 重庆和其美科技有限公司 | 一种含纳米金抗菌剂的制备方法 |
CN108310380A (zh) * | 2018-05-07 | 2018-07-24 | 临沂大学 | 一种石墨烯-金纳米花复合材料及其制备方法和应用 |
-
2020
- 2020-06-11 CN CN202010529936.9A patent/CN111632141A/zh not_active Withdrawn
- 2020-08-10 WO PCT/CN2020/108169 patent/WO2021248674A1/zh active Application Filing
-
2021
- 2021-06-08 NL NL2028410A patent/NL2028410B1/en active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103551194A (zh) * | 2013-11-14 | 2014-02-05 | 厦门大学 | 石墨烯-血红素及纳米金三元复合材料及制备方法与应用 |
CN104597240A (zh) * | 2015-02-02 | 2015-05-06 | 广西医科大学 | 石墨烯/类过氧化物酶双信号放大检测白血病的生物传感方法 |
CN107314981A (zh) * | 2017-07-31 | 2017-11-03 | 河南大学 | 基于hemin‑石墨烯复合材料分析检测PARP活性的方法 |
CN111505077A (zh) * | 2020-04-26 | 2020-08-07 | 桂林电子科技大学 | 一种基于RGO-Hemin/Au NPs纳米复合材料检测GPC3的方法 |
Non-Patent Citations (7)
Title |
---|
DONG HAIJIAO, ZHANG CHI;FAN YAO-YAO;ZHANG WEI;GU NING;ZHANG YU: "Nanozyme and Their ROS Regulation Effect in Cells", PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS, vol. 45, no. 2, 31 December 2018 (2018-12-31), pages 105 - 117, XP055878722, DOI: 10.16476/j.pibb.2017.0460 * |
GU CHANG-JIE, KONG FEN-YING, CHEN ZHI-DONG, FAN DA-HE, FANG HAI-LIN, WANG WEI: "Reduced Graphene Oxide-Hemin-Au Nanohybrids: Facile One-Pot Synthesis and Enhanced Electrocatalytic Activity towards the Reduction of Hydrogen Peroxide,", BIOSENSORS AND BIOELECTRONICS, vol. 78, 14 November 2015 (2015-11-14), Amsterdam , NL , pages 300 - 307, XP009532745, ISSN: 0956-5663, DOI: 10.1016/j.bios.2015.11.035 * |
HAN XIAOBO, ZHENG YINGHONG;YANG LIMING: "Advancement of Photosensitizers for Photodynamic Therapy", JOURNAL OF SHANGHAI UNIVERSITY (NATURAL SCIENCE EDITION), vol. 23, no. 2, 30 April 2017 (2017-04-30), pages 169 - 178, XP055878726, ISSN: 1007-2861, DOI: 10.3969/j.issn.1007-2861.2017.01.007 * |
LI JIANG, HAN SHUAI, WANG CHAO, SHI CHENG-CHENG, YIN YAO-BING: "Preparation of Hemin-NH 2 -Graphene and Its Dye Degradation Performance", HUAXUE SHIJI - CHEMICAL REAGENTS, BEIJING : HUAXUE HUAXUE SHIJI KEJI QINGBAO ZHONGXINZHAN, CN, vol. 42, no. 6, 20 April 2020 (2020-04-20), CN , pages 617 - 621, XP055878724, ISSN: 0258-3283, DOI: 10.13822/j.cnki.hxsj.2020007448 * |
LIU JING, MEIRONGCUI, LI NIU, HONGZHOU, SHUSHENG ZHANG: "Enhanced Peroxidase-Like Properties of Graphene-Hemin-Composite Decorated with Au Nanoflowers as Electrochemical Aptamer Biosensor for the Detection of K562 Leukemia Cancer Cells", CHEMISTRY-A EUROPEAN JOURNAL, vol. 22, 12 December 2016 (2016-12-12), pages 18001 - 18008, XP055878938, DOI: 10.1002/chem.201604354 * |
LUO CHENG, LI YAN, LONG JIANGANG: "Recent advances in applications of nanoparticles as enzyme mimetics", ZHONGGUO KEXUE. HUAXUE - SCIENTIA SINICA CHIMICA, ZHONGGUO KEXUE ZAZHISHE, CN, vol. 45, no. 10, 1 October 2015 (2015-10-01), CN , pages 1026 - 1041, XP055878713, ISSN: 1674-7224, DOI: 10.1360/N032015-00058 * |
WU ZHIFU, WANG ZUO-LIN: "The Influence of Graphene Oxide Lateral Size and Solution Concentration on Its Antibacterial Effect", JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, vol. 29, no. 1, 28 February 2019 (2019-02-28), pages 23 - 29, XP055878717, ISSN: 1005-4979, DOI: 10.3969/j.issn.1005-4979.2019.01.004 * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114010619A (zh) * | 2021-11-30 | 2022-02-08 | 江南大学 | 一种功能性纳米平台的构建及应用 |
CN114010619B (zh) * | 2021-11-30 | 2022-07-19 | 江南大学 | 一种功能性纳米平台的构建及应用 |
CN114669312A (zh) * | 2022-02-23 | 2022-06-28 | 东南大学 | 一种整合酶的制备方法 |
CN114669312B (zh) * | 2022-02-23 | 2023-10-27 | 东南大学 | 一种整合酶的制备方法 |
CN114505070A (zh) * | 2022-04-02 | 2022-05-17 | 陕西师范大学 | 多孔纳米酶、多孔纳米酶晶体及其制备方法和应用 |
CN114505070B (zh) * | 2022-04-02 | 2024-02-02 | 陕西师范大学 | 多孔纳米酶、多孔纳米酶晶体及其制备方法和应用 |
CN114713261A (zh) * | 2022-04-08 | 2022-07-08 | 国科温州研究院(温州生物材料与工程研究所) | 一种多功能纳米酶、制备方法及其应用 |
CN115121259A (zh) * | 2022-05-10 | 2022-09-30 | 陕西师范大学 | 氧化亚铜@金纳米模拟酶及制备方法和应用 |
CN115121259B (zh) * | 2022-05-10 | 2024-03-22 | 陕西师范大学 | 氧化亚铜@金纳米模拟酶及制备方法和应用 |
CN115121277A (zh) * | 2022-07-05 | 2022-09-30 | 合肥工业大学 | 一种碘掺杂单原子纳米酶CoCNI及其制备方法和应用 |
CN115121277B (zh) * | 2022-07-05 | 2024-01-09 | 合肥工业大学 | 一种碘掺杂单原子纳米酶CoCNI及其制备方法和应用 |
CN115646486A (zh) * | 2022-11-10 | 2023-01-31 | 辽宁大学 | 一种石墨烯负载钯纳米酶及其制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
NL2028410B1 (en) | 2021-12-01 |
CN111632141A (zh) | 2020-09-08 |
NL2028410A (en) | 2021-08-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2021248674A1 (zh) | 一种抗菌纳米酶及其制备方法 | |
Shan et al. | Cu2MoS4 nanozyme with NIR‐II light enhanced catalytic activity for efficient eradication of multidrug‐resistant bacteria | |
Wang et al. | Biodegradable nickel disulfide nanozymes with GSH-depleting function for high-efficiency photothermal-catalytic antibacterial therapy | |
Li et al. | Synergistic lysozyme‐photodynamic therapy against resistant bacteria based on an intelligent upconversion nanoplatform | |
Padmavathy et al. | Enhanced bioactivity of ZnO nanoparticles—an antimicrobial study | |
Kora et al. | Superior bactericidal activity of SDS capped silver nanoparticles: synthesis and characterization | |
Zardini et al. | Microbial toxicity of ethanolamines—Multiwalled carbon nanotubes | |
Zhao et al. | Multifunctional therapeutic strategy of Ag-synergized dual-modality upconversion nanoparticles to achieve the rapid and sustained cidality of methicillin-resistant Staphylococcus aureus | |
Buteică et al. | THE ANTI-BACTERIAL ACTIVITY OF MAGNETIC NANOFLUID: Fe 3 O 4/OLEIC ACID/CEPHALOSPORINS CORE/SHELL/ADSORPTION-SHELL PROVED ON S. AUREUS AND E. COLI AND POSSIBLE APPLICATIONS AS DRUG DELIVERY SYSTEMS. | |
CN114306382B (zh) | 一种铜基纳米酶及其制备方法和应用 | |
CN113234436B (zh) | 一种近红外碳量子点/二氧化硅复合材料及其制备方法和应用 | |
Bharti et al. | Enhanced antibacterial activity of decahedral silver nanoparticles | |
WO2023143052A1 (zh) | 三氧化二铋作为杀菌剂的应用 | |
CN106880842A (zh) | 一种硫化铜纳米材料的制备方法及应用 | |
Mirhosseini | Evaluation of antibacterial effect of magnesium oxide nanoparticles with nisin and heat in milk | |
CN114451511A (zh) | 一种抗菌纳米颗粒及其制备方法和应用 | |
Ramani et al. | Preliminary investigations on the antibacterial activity of zinc oxide nanostructures | |
Kong et al. | A Novel Z‐Scheme Heterostructured Bi2S3/Cu‐TCPP Nanocomposite with Synergistically Enhanced Therapeutics against Bacterial Biofilm Infections in Periodontitis | |
Al Attas et al. | Bactericidal efficacy of new types of magnesium hydroxide and calcium carbonate nanoparticles | |
CN113198494A (zh) | 一种光催化抗菌氯氧化铋/石墨烯二维异质结及其制备方法与应用 | |
CN116270480A (zh) | 一种咖啡酸金属多酚包覆金属有机骨架纳米粒子及其制备方法和应用 | |
ES2928009B2 (es) | Recubrimiento fotocatalítico con propiedades antimicrobianas | |
CN111841599A (zh) | 一种具有光催化抗菌性能的碳量子点掺杂氮化碳复合纳米材料及其制备方法与应用 | |
CN112715573A (zh) | 一种抑菌性好的介孔核壳微球的制备方法 | |
CN114891346B (zh) | 一种基于钼多酸的聚赖氨酸复合物及其在抗菌领域中的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20939940 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 20939940 Country of ref document: EP Kind code of ref document: A1 |
|
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC |