CN111642518A - 在有机材料存在下具有改善的稳定性的碘载体组合物 - Google Patents
在有机材料存在下具有改善的稳定性的碘载体组合物 Download PDFInfo
- Publication number
- CN111642518A CN111642518A CN201911363345.2A CN201911363345A CN111642518A CN 111642518 A CN111642518 A CN 111642518A CN 201911363345 A CN201911363345 A CN 201911363345A CN 111642518 A CN111642518 A CN 111642518A
- Authority
- CN
- China
- Prior art keywords
- thiocyanate
- composition
- iodide
- iodophor
- potassium
- 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 56
- 239000011368 organic material Substances 0.000 title abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 21
- 239000011630 iodine Substances 0.000 claims abstract description 21
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 20
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 60
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 41
- -1 iodate ions Chemical class 0.000 claims description 30
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 28
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 26
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 21
- 241000700605 Viruses Species 0.000 claims description 17
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 claims description 16
- 239000008267 milk Substances 0.000 claims description 15
- 235000013336 milk Nutrition 0.000 claims description 15
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- 150000002978 peroxides Chemical class 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 230000001580 bacterial effect Effects 0.000 claims description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- LOMPYPGVYNRXCJ-UHFFFAOYSA-N iodo thiocyanate Chemical class ISC#N LOMPYPGVYNRXCJ-UHFFFAOYSA-N 0.000 claims description 9
- 229940116357 potassium thiocyanate Drugs 0.000 claims description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- 208000004396 mastitis Diseases 0.000 claims description 8
- 239000012286 potassium permanganate Substances 0.000 claims description 8
- 239000000499 gel Substances 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- QVQLCTNNEUAWMS-UHFFFAOYSA-N barium oxide Chemical compound [Ba]=O QVQLCTNNEUAWMS-UHFFFAOYSA-N 0.000 claims description 6
- 239000000839 emulsion Substances 0.000 claims description 6
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 claims description 6
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- JLKDVMWYMMLWTI-UHFFFAOYSA-M potassium iodate Chemical compound [K+].[O-]I(=O)=O JLKDVMWYMMLWTI-UHFFFAOYSA-M 0.000 claims description 6
- 239000001230 potassium iodate Substances 0.000 claims description 6
- 235000006666 potassium iodate Nutrition 0.000 claims description 6
- 229940093930 potassium iodate Drugs 0.000 claims description 6
- DTMHTVJOHYTUHE-UHFFFAOYSA-N thiocyanogen Chemical compound N#CSSC#N DTMHTVJOHYTUHE-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- MWNQXXOSWHCCOZ-UHFFFAOYSA-L sodium;oxido carbonate Chemical compound [Na+].[O-]OC([O-])=O MWNQXXOSWHCCOZ-UHFFFAOYSA-L 0.000 claims description 5
- 241000233866 Fungi Species 0.000 claims description 4
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- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 claims description 4
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- XQPRBTXUXXVTKB-UHFFFAOYSA-M caesium iodide Chemical compound [I-].[Cs+] XQPRBTXUXXVTKB-UHFFFAOYSA-M 0.000 claims description 4
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical group OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims description 4
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- JGASTEWEWNVFRL-UHFFFAOYSA-N 2-azanylidyne-n-sulfidoacetonitrilium Chemical compound [S-][N+]#CC#N JGASTEWEWNVFRL-UHFFFAOYSA-N 0.000 claims description 3
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 3
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- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 3
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- 229910000043 hydrogen iodide Inorganic materials 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 3
- HPGPEWYJWRWDTP-UHFFFAOYSA-N lithium peroxide Chemical compound [Li+].[Li+].[O-][O-] HPGPEWYJWRWDTP-UHFFFAOYSA-N 0.000 claims description 3
- ZJZXSOKJEJFHCP-UHFFFAOYSA-M lithium;thiocyanate Chemical compound [Li+].[S-]C#N ZJZXSOKJEJFHCP-UHFFFAOYSA-M 0.000 claims description 3
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- 150000004965 peroxy acids Chemical class 0.000 claims description 3
- KXAHUXSHRWNTOD-UHFFFAOYSA-K rhodium(3+);triiodide Chemical compound [Rh+3].[I-].[I-].[I-] KXAHUXSHRWNTOD-UHFFFAOYSA-K 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
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- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 claims description 3
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- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 claims description 3
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- 229910052792 caesium Inorganic materials 0.000 claims description 2
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 2
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- NALMPLUMOWIVJC-UHFFFAOYSA-N n,n,4-trimethylbenzeneamine oxide Chemical compound CC1=CC=C([N+](C)(C)[O-])C=C1 NALMPLUMOWIVJC-UHFFFAOYSA-N 0.000 claims description 2
- BBCHGPOXBBSEMV-UHFFFAOYSA-K rhodium(3+);trithiocyanate Chemical compound [Rh+3].[S-]C#N.[S-]C#N.[S-]C#N BBCHGPOXBBSEMV-UHFFFAOYSA-K 0.000 claims description 2
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Abstract
本发明的名称是在有机材料存在下具有改善的稳定性的碘载体组合物。本发明涉及药学和工业碘载体制剂,其合成和潜在应用。该化合物具有可预测的抗菌活性。此外,在有机材料存在下,该碘载体比传统的碘载体稳定得多。当在溶液中时该组合物释放提供抗菌活性的游离碘。
Description
本申请为分案申请,原申请的申请日是2015年8月20日、申请号是201580055477.2、 发明名称为“在有机材料存在下具有改善的稳定性的碘载体组合物”。
发明背景
本发明涉及药学和工业碘载体制剂,其合成和潜在应用。该化合物具有可预测的抗菌 活性。此外,该碘载体在有机材料存在下比传统的碘载体稳定得多。碘载体是与稳定剂复 合的基于碘的化合物。当在溶液中时它们释放游离碘,其提供抗菌活性。它们通常通过使 碘与稳定剂混合伴随加热制备。
由于游离碘与主要细菌蛋白相互作用,引起抑菌或杀菌效果,碘载体发挥抗菌活性。 它们具有潜在的宽范围的用途,从清洁和消毒工业或医疗,至创伤治疗(在感染之后或之前 作为预防药)。稀释的碘载体被广泛地用于乳品工业中以清洁机器,最小化潜在致病生物体 的传播。碘载体不仅是抗菌的,而且还是强力抗病毒的和抗真菌的。它们的使用需要非常 少的后冲洗,这与基于次氯酸盐的漂白化合物不同。它们通常在水生池塘中用作最小化细 菌或寄生生物体的过量生长的方法。它们可用于杀死与痤疮和皮肤状况相关的病原体生物 体,以及治疗疱疹感染(病毒)的突然爆发。碘载体已经被使用了许多年,并且通常被认为 是安全的化合物。基于可获得的毒理学数据的综述,美国环保署推断“通过口服、皮肤和 吸入路径的暴露,碘和碘载体复合物具有非常低的毒性”。最常见的碘载体是聚乙烯吡咯 烷酮碘(已知为PVP-碘、PVP-I或聚维酮,和其商标名Betadine或Wokadine)。PVP聚合物 也用来降低碘的潜在毒性效果。存在非常少的报道的细菌对碘介导的杀死的抗性/耐受性特 征。这更可能是由于碘载体对细胞内各种细菌蛋白的任意靶向。这种耐受性/抗性表型将需 要细菌基因组中的多个并且同时有益的突变。
PVP-I的使用已经克服了碘酊和鲁戈氏液(Lugol’s solution)(碘与碘化物离子的溶液)关 于长期储存、游离碘对总的碘和毒性问题等的缺点中的一些。然而,常用的碘载体比如 PVP-I在有机材料存在下是非常不稳定的。在将PVP-I溶解在水中之后,化合物发挥显著 的抗菌活性,但是在有机物质存在下抗菌活性最低。例如,PVP-I在水中对大肠杆菌ATCC 25922的最低抑菌浓度(MIC)是<1mg L-1。在富有机生长介质(比如溶原性肉汤)中重复测试 之后,在>500mg L-1记录MBC值。MBC值的差异指示传统碘载体的限制。在许多环境中这种浓度的使用实际上将是困难的、过分地昂贵的和潜在地有毒的。
在乳品工业中,PVP-I定期地被用于在挤奶之前和之后清洁母牛的乳头以杀死存在的 细菌。然而,如果PVP-I与牛奶接触,活性被快速减弱。相同模式出现在其他工业中,比如烘焙等,这是由于留在机器上的食品残渣可与PVP-I相互作用并且停止其抗菌作用。
发明目的
本发明的目的是提供新的碘载体,其在有机材料存在下比传统的碘载体稳定得多。进 一步目的是提供产生碘载体的组合物,尤其是可用于消毒具有高有机物质负载的环境的组 合物。
发明内容
根据本发明,提供了一种产生碘载体的组合物,其包括碘化物或碘酸盐离子、硫氰酸 盐离子和氧化剂。
碘化物/碘酸盐的来源可以是碘化钾、碘化钠、碘化锂、碘化铯、碘化氢、碘化铑、或缓释形式的碘化物、碘酸钾或碘酸钠。
硫氰酸盐离子的来源可以是硫氰酸钾、硫氰酸锂、硫氰酸铯、硫氰酸(hydrogenthiocyanate)、硫氰酸铑、缓释形式的硫氰酸盐、或氰酸化合物比如氰酸钾或硫化氰。
氧化剂可以是过氧化氢或高锰酸钾;过氧化钠;过氧化锂;释放过氧化物的过碳酸盐; 释放过氧化物的柠檬酸或维生素C;过氧化物盐,包括氧化钡、过硼酸钠、过氧化氢-尿素 加合物;释放氧的假过氧化物,其包括超氧化物、二氧(dioxygenals)、臭氧、臭氧化物;有机过氧化物,其包括过氧酸、卤化酰基和脂肪族过氧化物。
在一些实施方式中,碘酸钾可用作氧化剂和碘酸盐/碘离子的来源。
本发明还提供包括碘-硫氰酸盐复合物的碘载体,该碘-硫氰酸盐复合物包含氧,比如 I2OHS(CN)2。
新的碘载体可以通过在水性环境中混合碘化物离子的来源(比如碘化钾)、硫氰酸盐离 子的来源(比如硫氰酸钾)和氧化剂比如过氧化氢制备。强力抗菌化合物可以通过混合1% w/v硫氰酸钾(KSCN)、1%w/v碘化钾(KI)和1%w/v过氧化氢(H2O2)制备。碘载体的更稀 释或浓缩的溶液可以通过增加或减少起始组分而制备。同样地,可以制备浓缩的原料,并 且根据需要相应地稀释。
在该水性环境中,碘化物和硫氰酸盐同时被氧化,并且形成包含氧原子的碘-硫氰酸盐 复合物。进一步氧化可发生,产生I2、I3、I4和I5种类,增加了分子量。
过氧化氢的使用是有利的,因为当其裂解以形成氧和水时不存在显著的分解或毒性问 题。可以使用其他氧化剂,例如高锰酸钾,尽管它们确实添加不需要的颜色和杂质至环境。 可选地,碘酸钾(KIO3,1%w/v)可用作氧化剂和碘来源二者,作为过氧化物和碘化物的组 合的可选方案。它和硫氰酸盐之间的反应以(在本文描述的浓度下需要几乎24小时,尽管 反应可以通过添加过氧化氢被加速)较慢的速率进行。重要地,基于碘酸盐的反应需要组分 的高于1%w/v的浓度以产生显著的抗菌活性。使用碘化物/硫氰酸盐/过氧化物模型,溶液 可以使用低得多(0.001-0.01%w/v)或高得多的浓度制造,并且发挥的抗菌活性将与浓度具 有线性关系,这与碘酸盐模型不同。这是出人意料的。碘载体——如果在水性环境中制备 ——可被缓冲至需要的pH。它在多种盐存在下,并且如果在密封环境中在相对大的温度范 围下是稳定的。碘载体可以被制备为水凝胶(使用例如1%w/v聚丙烯酸钠)。这使得其本身 被作为用于烧伤/皮肤疾病的凝胶使用。
5-20ml体积的0.5-2%w/v制备的碘载体将能够被注入乳腺炎反刍动物的乳房内和杀 死病原体生物体。治疗方案可反映抗生素治疗(对乳腺炎动物一天一次或两次,持续2-10 天)。因为由碘载体发挥的宽范围的抗菌活性谱,化合物将能够杀死各种细菌(包括革兰氏 阳性、革兰氏阴性、抗生素抗性细菌、真菌菌株和病毒)。
稀释形式(<0.1%w/v)的新的碘载体可用于治疗小伤口或擦伤。更加浓缩形式的相同碘 载体可用于治疗更严重的皮肤感染(~0.5%w/v)。雾化的喷雾形式的碘载体可适用于治疗其 中抗生素使用通常不成功的肺感染。这种递送机制还将在具有如下可能性:在开放创伤出 现的手术中作为预防药的手段。浓缩形式(>1%w/v)可用于清洁/杀菌或净化无生命的材料, 比如食品加工装置、钢碗、外科手术装置等。
虽然优选的是使用简单的离子盐,比如碘化物和硫氰酸盐的钾或钠变型,但是也可以 使用其他形式,包括但不限于碘化钠、碘化钾、碘化锂、碘化铯、碘化氢、碘化铑、或通过元素碘的氧化和作为硫氰酸盐的来源;硫氰酸钾、硫氰酸锂、硫氰酸铯、硫氰酸氢、硫 氰酸铑、或氰酸化合物比如氰酸钾或硫化氰。
同样地,将过氧化氢用作氧化溶液是优选的,这是因为其在需要的浓度(<3%w/v)下是 无毒的,并且不留下显著的残余物。可以使用可替代的较不优选的氧化剂,包括但不限于 过氧化钠;过氧化锂或释放过氧化物的过碳酸盐;释放过氧化物的柠檬酸或维生素C;过 氧化物盐,其包括氧化钡、过硼酸钠、过氧化氢-尿素加合物;释放氧的假过氧化物,其包括超氧化物、二氧、臭氧和臭氧化物;有机过氧化物,其包括过氧酸、卤化酰基、脂肪族 过氧化物。
碘载体可以制备为适合使用的凝胶、乳液、油、水凝胶、液体或粉末。化合物可以被冻干并且储存为干燥形式以延长储存。化合物可以作为干燥(和随后润湿)或湿润产品添加至绷带,作为预防或杀死细菌感染的手段。化合物可适合于口服递送、静脉内递送、外用 递送、肠内或肠胃外递送、或通过吸入递送。化合物可以与常规的药学上可接受的载体和 赋形剂一起配制。适合的载体和赋形剂包括但不限于粘合剂、包衣、颜料、崩解剂、香料、 抗结合剂、助流剂、润滑剂、防腐剂、吸着剂、甜味剂或媒介物。
碘化物与硫氰酸盐(按重量计)的0.1:10-10:1的比值范围在产生显著数量的游离的可利 用的碘以及氧化的硫氰酸盐稳定剂中是重要的。更优选的比值是0.2:1-5:1。更优选的比值 是0.8:1-1.2:1。更优选的选择还是硫氰酸盐与碘化物的1:1的比值。例如,碘化钾和硫氰 酸钾中每种为1,000mg L-1,在充当氧化剂——800-1200mg L-1——的足够的过氧化氢存在 下。
过氧化氢与碘化物/硫氰酸盐(按重量计)的0.25:1-4:1的比值范围足以允许同时氧化和 由此产生碘载体。过氧化氢与碘化物/硫氰酸盐的更优选的选择是0.5:1-2:1。过氧化氢与 碘化物/硫氰酸盐的更优选的选择还为1:1的比值。在过氧化氢与碘化物/硫氰酸盐的比值为 2:1或更大时,化合物由于pH改变较不稳定,并且由于硫氰酸盐SCN键断裂,可导致形 成非期望的CN和SO4。在过氧化氢与碘化物/硫氰酸盐的<1:1的范围内,活性由于发生不 充分的氧化而降低。
过碳酸盐是干燥的化合物,其在与水性环境混合时释放过氧化氢。这样,过碳酸钠(和 其他)可充当过氧化氢的来源。基于来自过碳酸盐的可利用的过氧化氢的简单计算将允许液 体过氧化物与干燥过碳酸盐的简单交换。此外,氧化和释放游离O的其他化合物可以用于 测定可能达到的游离O含量。简单的氧化还原酶能够与单糖反应以产生过氧化氢的来源。 通过滴定在该环境中产生的正确水平的过氧化氢可以使用这种系统。
出人意料的是,在有机材料存在下使用硫氰酸盐提供这种稳定。SCN是线型化合物。 它不是提供特性基础的特定原子。烯丙基异硫氰酸盐不足以产生相同的结果,这表明该反 应非常依赖于接近原子。多种包含硫(S)的化合物——包括各种硫酸盐、硫醇和硫基化合物 比如甲硫氨酸——不允许以相同的方式产生有机-材料-稳定的碘载体。同样地,多种基于 氰酸的化合物比如二氯异氰脲酸钠或氰酸钾在允许产生有机-材料-稳定的碘载体上也不是 有效的。这使得使用硫氰酸盐的结果都是更出人意料的和新的。
取决于氧化程度和相对浓度,许多潜在碘硫氰酸盐化合物被产生和释放,从每个分子 单个碘直到七个碘原子。这种化合物是ISCN、I2SCN、I2(SCN)2、IOH(SCN)2、I3OH(SCN)2、I3OH(SCN)3、I4(SCN)4OH、I5(SCN)5。
通过碘化物/碘酸盐离子(以允许碘的形成)和硫氰酸盐离子的同时氧化在溶液中产生本 发明的碘载体,其用来使所得的抗菌活性碘稳定。所得的碘载体是碘-硫氰酸盐复合物类化 合物。根据需要,其可以被制备为稀释的或更浓缩的制剂。新的碘载体可以通过碘化物/ 碘酸盐和硫氰酸盐离子(在适当的氧化剂,例如过氧化氢存在下)的混合在原位制备,或在 非原位制备,并且被相应地施加/添加。与其他碘载体一样,其在基于水的环境中发挥强力 的抗菌活性。然而,用于溶原性肉汤(LB)中的大肠杆菌ATCC25922的MIC仍然低于10mg L-1,这与PVP-I的MIC不同(500mg L-1)。
该新的碘载体作为抗菌剂具有许多潜在用途,其中已经使用传统的碘载体,即,创伤 /烧伤治疗、抗病毒外用治疗、机器消毒剂、皮肤擦拭、抗真菌外用药剂。此外,新的碘载体适合于许多潜在用途,而传统的碘载体化合物由于有机材料的存在将不适合。这种环境的实例包括如用于反刍动物的乳腺炎治疗,其中化合物被用作存在牛奶的乳房中抗生素的可选方案。进一步实例是用于“清洁”未处理的牛奶,用于消灭约内氏病的病原体生物体,其可在牛奶中从母体转移至小牛。新的碘载体可用于延长没有足够制冷的区域中的牛奶的储存期。由于与牛奶接触后抗菌活性的快速损耗,用传统的碘载体这是不可能的。此外, 新的碘载体更适合于传统应用,由于它不容易被任何存在的有机材料(创伤中的脱落的细胞、挤奶机器上的有机碎片等)损耗。另外,碘载体具有作为抗生素治疗的替代方案的潜在用途,外用地、口服地或静脉内地。其可用作皮肤消毒剂、手术前皮肤制剂、外用应用、 眼睛治疗、耳朵治疗、痤疮治疗、病毒感染的治疗或用于牙科环境,例如抗龋齿或抗牙斑 冲洗剂、程序前冲洗剂或牙髓的消毒。化合物还用于食品消毒制剂中;或环境应用中,例 如表面、管线的消毒;水的消毒(比如用化合物浸渍过滤器等)。化合物具有替代聚维酮碘 的使用的可能性,其活性优于聚维酮碘。
碘载体还可用于癌症治疗,其中在例如乳腺癌中其可用于替代分子碘I2的使用(Anguiano等人.Thyroid.第17卷,第9期,2007,第851-859页)。
附图说明
图1:鲁戈氏液(上)和新的碘载体(下)对牛奶颜色的影响(以500mg L-1开始从左至右二 倍稀释)。
图2:在212、232、309、386、426、483、580、669、746、796、843和959处可观 察到1%(1:1).m/z峰的飞行时间质谱(TOF-MS)分析。
图3:雾化模拟的装配。
图4:雾化模拟的装配。
图5:雾化的化合物针对大肠杆菌的杀死效率。
图6:雾化的化合物针对铜绿假单胞菌的杀死效率。
具体实施方式
组合物的实施例
1.包含1-100,000mg L-1碘载体的一般洗液/抗菌组合物,其用作抗菌的外用软膏/乳 剂/凝胶/溶液。
2.包含10-10,000mg L-1碘载体的一般洗液/抗菌组合物,其用作抗菌的外用软膏/乳 剂/凝胶/溶液。
3.包含10-10,000mg L-1碘载体的组合物,其用作使用雾化溶液的吸入抗菌疗法。
4.浸泡在或包含10-10,000mg L-1碘载体的绷带,其用作抗菌绷带。
5.用于治疗反刍动物的乳腺炎的组合物,其包含10-10,000mg L-1碘载体,所述组合 物作为每天一次或两次治疗的乳房内注入物。
6.每天一次或每天两次的临时的抗菌组合物,治疗通过乳房内设备完成,所述组合 物包含能够原位产生如上所述的10-10,000mg L-1碘载体组分(碘化物或碘酸盐阴离子在 10-10,000mg L-1之间,硫氰酸盐离子在10-10,000mg L-1之间,并且氧化溶液(如果需要) 比如过氧化氢在10-1,000mg L-1之间)。
7.临时的抗菌(和抗生物膜)组合物——一般洗液,其包含能够原位产生如上所述的 10-1,000mg L-1碘载体的组分(碘化物或碘酸盐阴离子在10-10,000mg L-1之间,硫氰酸盐离 子在10-10,000mg L-1之间,并且氧化溶液(如果需要)比如过氧化氢在10-10,000mgL-1之 间),出于先前实施例中描述的任何目的。
8.如实施例1-7中描述的组合物,其中氧化溶液选自本文中其他地方描述的列表,包 括但不限于过氧化氢,并且以足够的浓度存在以允许硫氰酸盐和碘化物(或碘酸盐)离子的 氧化。
药学上有效的载体是水、生理盐水、乳液、凝胶或水凝胶。
组合物可适合于通过浸湿的绷带递送。
组合物可适合于用作抗菌鼻冲洗剂、抗菌剂漱口水、抗真菌洗液,作为消毒剂被添加 至用于治疗创伤或烧伤感染的绷带或泥罨剂,或以喷雾的形式被雾化,用于治疗人或动物 肺的细菌或真菌感染。
本发明还提供涂布如上所述的组合物的医疗设备,和浸渍该组合物的绷带或泥罨剂。
在任何先前的实施例中描述的组合物,其中其作为抗菌剂以10-10,000mg L-1的浓度被 补充至被污染的牛奶,用于消灭细菌,比如鸟型副结核分枝杆菌(mycobacteriumavium paratuberculosis)。
在任何先前的实施例中描述的组合物,其中其作为抗菌剂以10-10,000mg L-1的浓度被 补充至被污染的环境,用于消灭真菌、寄生虫、单细胞生物体、病毒、或细菌/真菌孢子。
随着将PVP聚合物引入化合物,可以产生更稳定形式的碘-硫氰酸盐碘载体。重要地, 与包含碘的PVP-I混合的硫氰酸盐不用来改变已有PVP-I的结构,表明新的碘载体不能以 该方式被制备。
Vince:将Paul的鸡蛋浸渍(egg dipping)的工作的实例作为食品制备用途的实施例?
实施例9
通过将10g碘化钾、10g硫氰酸钾添加至大约950ml的水制备1L批量的碘载体。当盐完全溶解时,将33.33ml的30%过氧化氢添加至溶液。然后用水将溶液定容至1,000ml。可以调节溶液的pH并且根据需要缓冲至5.5。该溶液自此被称为1%(1:1)混合物,该比值指添加的过氧化物的重量与使用的硫氰酸盐和碘化物盐的重量的比值。
使用过氧化氢的替代方案是使用大约33g的过碳酸钠(具有30%可利用的过氧化氢), 并且允许完全溶解以允许过氧化物的释放。
作为进一步的替代方案,通过将10g碘酸钾和10g硫氰酸钾添加至大约950ml制备1L批量的碘载体。然后用水将溶液定容至1,000ml,并且放置24小时,以使得反应发生。 然后可以调节溶液的pH并且根据需要缓冲至5.5。
新的碘载体可进一步与PVP聚合物复合,使得在存在实施例中描述的碘载体的有机材 料的情况下,其具有除了稳定性以外的PVP-I两者的优势。
适当的糖皮质激素可被补充至预定用于乳腺炎动物的乳房内注入物,或以雾化/一般洗 液的形式预定用于肺感染的治疗或预防,以帮助潜在局部耐受问题。类固醇可以是(但不限 于)每剂量在5和50mg之间存在的氢化可的松/皮质醇、去氢氢化可的松或强的松。
实施例10
根据图3装配两个漏斗、60mL注射器、橡胶管道和雾化器。通过将一片纱布放置在一段胶带上,并且根据图4将绷带并且粘附在纱布上,绷带片被悬挂在两个漏斗的中间。 使用具有无菌尖端的自动加样器将500μL靶细菌(大肠杆菌ATCC 25922或铜绿假单胞菌) 施加至绷带片上。两个漏斗关闭在一起,形成790mL的区域体积(同时注射器被伸展),并 且石蜡膜被施加在其边缘周围以便使装置关闭密封并且保持内部环境是气密的。选择1ml 的化合物放置在雾化室(nebuliser chamber)内,然后关闭该室。开启雾化器(由Aerogen Ltd.制造的Aeroneb Pro-X Solo雾化器系统)以开始化合物的雾化,然后将接种的绷带暴露于该 室中1ml的雾化的化合物持续15分钟。在暴露于化合物15分钟之后,将接种的绷带悬挂在无菌通用管中10ml的1%PBS溶液中。在施加每种化合物之间,通过使1ml的无菌H2O 通过其来清洁雾化器。摇动该管并且放置在涡流(vortex)上以便释放包含在绷带中的细菌细胞至溶液中。从PBS-大肠杆菌溶液中取出20μL样品并且使用96孔板,进行10倍稀释, 直到获得10-4的稀释液。20μL的每个稀释液无菌地扩散至溶原性琼脂平板上。平板在37℃ 下培养过夜。计算可回收的大肠杆菌的总的活菌数。对于下述化合物中的每种进行该方案: 1%H2O2+1%KI+1%KSCN(标记为1mg SAC)、0.1%H2O2+0.1%KI+0.1%KSCN(0.1mg SAC)、0.1mg庆大霉素、1mg庆大霉素、0.01mg左氧氟沙星、0.1mg左氧氟沙星、1mg 左氧氟沙星、10mg左氧氟沙星、0.01mg多黏菌素B、0.1mg多黏菌素B、1mg多黏菌素 B、0.1mg H2O2、1mg H2O2、10mgH2O2。如图5和6中所显示,本发明的新的碘载体显 示针对大肠杆菌ATCC 25922的卓越的杀死效率。它显示了对测试的包括左氧氟沙星和多 黏菌素B(在所有浓度下)的几种抗生素的等效性能。证明了新的碘载体在杀死微生物上优 于庆大霉素(在0.1mg和1mg两种浓度下)。新的碘载体显示针对铜绿假单胞菌卓越的杀死 效率,在测试的所有浓度下杀死大于90%。除了10mg浓度下的左氧氟沙星以外,这与测 试的所有抗生素形成对照。对于使用的所有其他抗生素和浓度,它们不能够杀死大于20% 的细菌。10mg浓度的左氧氟沙星在杀死铜绿假单胞菌上是有效的,然而,采用的浓度(10 mg)是非常高的剂量和其将进入溶液上限。针对两种生物体,可见甚至在采用的高浓度(10 mg)下,过氧化氢具有有限的杀死效率。因此,该实施例显示碘载体经雾化被递送的可能 性,同时保留极高程度的效能,尤其是针对铜绿假单胞菌——一种常见的呼吸道病原体。
结果
最低抑菌浓度
测试如实施例9中描述所产生的针对与皮肤、乳腺炎和肺感染相关的一系列微生物的 新的1%(1:1)的效能以确定其活性。为了进行这种效能测试,使用微量肉汤稀释方法进行 最低抑菌浓度(MIC)测试,其中将双倍稀释的化合物添加至生长介质中包含测试生物体 (105-6菌落形成单位ml-1)的孔中。然后在24小时内记录孔内含物的光密度。光密度的增加 指示测试生物体的生长。如果在37℃下在24小时内细菌在具体孔中未能生长,其中的浓度被认为是抑制的。抑制生长所需的最低浓度被称为MIC。对于涉及没有生长介质(即水和牛奶)的测试,来自孔的等分试样被传代培养至新鲜的营养琼脂(NA)。如果细菌随后未能从取样的整分试样生长,相应的化合物浓度被认为是抑制的。
如从表1清楚的是,碘载体(1%,1:1)在小于30mg L-1的浓度下对抑制每种生物体(包 括抗生素抗性生物体)是有效的。该活性水平接近低浓度下抗生素活性水平。作为比较, PVP-I和鲁戈氏碘在低于500-1,000mg L-1的浓度下对消除相同的细菌菌株是不成功的。这 是由于PVP-I或鲁戈氏-衍生的碘通过在生长介质中存在的有机材料的有害失活。MIC的这 种差别被标记在各种生长介质和奶环境中(对于碘-硫氰酸盐碘载体<30mg L-1和PVP-I/鲁 戈氏>500-1000L-1的MIC)。
表1:用于溶原性肉汤中的细菌菌株的碘-硫氰酸盐碘载体的最低抑菌浓度值
在没有任何生长介质(即生理盐水环境)的情况下,新的碘-硫氰酸盐碘载体、鲁戈氏液 和PVP-I的0.01-5mg L-1的比较浓度足以杀死相同的细菌菌株,表明相关活性的差异是由 于有机材料。
描述的组合物已经显示是杀菌的并且不抑菌。如果从环境去除抗菌化合物并且一旦细 菌/病毒/真菌/酵母菌再次开始增殖,化合物将被描述为抑菌的(即,使细胞停止生长)。如 果它们不恢复,则化合物将被归类为杀菌的(即,杀死细胞)。在用新的碘载体的测试中, 使用生理盐水中20mg L-1持续1小时,能生存的细菌细胞是不可恢复的,即使向生理盐水 添加丙酮酸钠来帮助细菌恢复。单独使用相同浓度(和进一步10倍更高浓度)的过氧化氢使 得能生存的细胞恢复,表明杀死不是过氧化物介导的。
抗病毒活性:测试如实施例9中描述产生的新1%(1:1)针对与各种人和动物疾病相关 的一系列病毒的效能,以确定其活性。使用许多不同的试验,以确定化合物潜在抗病毒活 性。这些包括:病毒致细胞病变作用(CPE)试验,由此测试化合物的其防止靶病毒在哺乳 动物细胞培养物中引起病毒致细胞病变作用的能力。将化合物稀释数倍(至多8倍稀释), 通过回归分析确定有效的抗病毒浓度。测试化合物的平行毒性。也进行病毒产率减少试验, 以确定化合物在哺乳动物细胞培养中抑制病毒产生的能力。该试验是两步骤试验,由此首 先在包含各种稀释的化合物的培养物中产生病毒,随后在96孔板中通过终点稀释滴定样 品的病毒滴度。通过回归分析确定有效的抗病毒浓度。
也进行杀病毒试验-这确定化合物是否可杀死细胞外部的病毒或使细胞外部的病毒失 活,即,是否通过接触化合物,病毒被失活并且不能感染细胞。该试验在显示环境设施中 具有潜能的化合物是重要的。通过用化合物培养病毒1小时进行该试验,随后通过在96孔板中终点稀释确定病毒滴度。这些研究的结果显示在下表中:
生物体 | MIC(mg/L) |
牛呼吸道合胞病毒(BRSV) | <200-300 |
1型牛疱疹病毒(BHV-1) | <200-300 |
3型牛副流感病毒(BPIV3) | <200-300 |
牛病毒性腹泻病毒(BVDv) | <200-300 |
细小病毒 | <200-300 |
副流感病毒 | <200-300 |
2型正黏病毒马流感A | <200-300 |
马-1型(H7N7)病毒 | <200-300 |
马-2型(H3N8)病毒 | <200-300 |
单纯性疱疹病毒-1型 | <200-300 |
单纯性疱疹病毒-2型 | <200-300 |
诺瓦克病毒(Norovirus) | <200-300 |
腺病毒 | <200-300 |
脊髓灰质炎病毒(1型和3型) | <200-300 |
轮状病毒 | <200-300 |
柯萨奇病毒 | <200-300 |
鼻病毒 | <200-300 |
风疹病毒 | <200-300 |
麻疹病毒 | <200-300 |
流感病毒 | <200-300 |
艾滋病病毒 | <200-300 |
腮腺炎病毒 | <200-300 |
测试如实施例9中描述产生的新1%(1:1)针对与各种人和动物疾病相关的一系列酵母 菌、霉菌和真菌的有效性,以确定其活性。根据临床实验室标准化协会(CLSI)开发和批准 的各种方案进行药敏试验,即,酵母菌药敏试验的CLSI M27-A2;通过平板扩散的酵母菌 药敏试验的CLSI M44-A;对于霉菌药敏试验的CLSI M38-A。这些研究的结果呈现在下表中:
生物体 | MIC(mg/L) |
疣状癣菌(Trichophyton verrucosum) | <200mg/l |
絮状表皮癣菌(Epidermophyton floccosum) | <200mg/l |
红色毛癣菌(Trichophyton rubrum) | <200mg/l |
指间毛癣菌(Trichophyton interdigitale) | <200mg/l |
断发毛癣菌(Trichophyton tonsurans) | <200mg/l |
须毛癣菌(Trichophyton mentagrophytes) | <200mg/l |
犬小孢子菌(Microsporum canis) | <200mg/l |
石膏样小孢子菌(Microsporum gypseum) | <200mg/l |
假丝酵母 | <200mg/l |
曲霉 | <200mg/l |
获得原生动物的类似的MIC。
新的碘载体的进一步的益处是相对缺少与其用途相关的染色和颜色。从在牛奶环境中 发挥的活性方面,鲁戈氏优于PVP-I(尽管活性比新的碘载体低约40倍)。然而,杀死细菌 所需的浓度也导致牛奶的外观和颜色的改变。新的碘载体没有这种情况。图1表明了在包 含500、250、125、62.5、31.25、15.625、7.8125、3.9和1.95mg L-1的每种化合物的牛奶 中的颜色改变(从左至右)。清楚地,鲁戈氏的碘产生橙色和甚至棕色着色(低至并且包括>10mg-1),而新的碘载体甚至在500mg L-1下也不这样。当对于乳腺炎或处理污染的牛奶供应使用适当剂量浓度时,这是重要的。
使用飞行时间质谱(TOF)检查1%(1:1)样品,以确定负责抗菌活性的复合物。确定了许 多感兴趣的峰(指示它们的质荷比-m/z)。m/z 121和922处的峰对应内标。这表明在反应期 间形成了多于一种的碘-硫氰酸盐复合物。随着更多的碘原子附着并且允许附着更多待附着 的氰分子,形成了许多更大的分子。在212、309、386、483的m/z处观察到峰。这些m/z值将相当于许多化合物,比如ICNH(SCN)、I2SCN、I2OH(SCN)2和I3SCHN2O。这些结构 的每一种是具有较小取代和加成的碘-硫氰酸盐复合物。在580、669和746的m/z比值处 确定了较弱的峰,并且959指示更多的碘原子和氰分子附着,产生甚至更大的复合物。
为了表明可采用进一步可选的氧化剂,以产生代替过氧化氢的化合物,在平板扩散试 验中使用高锰酸钾;小浓度的组分(10μl水中100μg的硫氰酸盐/碘化物/高锰酸钾)被施加 至用105cfu/ml的大肠杆菌ATCC 25922新鲜接种的溶原性琼脂的顶部的纸片。将平板在 37℃下培养过夜并且测量所得的抑制区域。大的区域指示强的抗菌活性。无区域指示没有 可感知的抗菌活性。来自测试的结果呈现在表2中。高锰酸盐本身可发挥抗菌作用,但是仅仅在没有有机材料存在下。所以,在包含高锰酸盐的样品中记录的任何抗菌活性是由于其氧化硫氰酸盐和碘化物,以产生新的碘载体。显然,当混合三种化合物时,记录了强的 活性,但是仅仅当混合所有三种时。所以,清楚地表明除了过氧化物之外的可选氧化剂能 够产生碘载体。
溶液 | 抑制区域 |
375μg KMnO<sub>4</sub> | 无区域 |
375μg KMnO<sub>4</sub>+375μg KSCN | 无区域 |
375μg KI+375μg KSCN | 无区域 |
375μg KMnO<sub>4</sub>+375μg KI+375μg KSCN | 34mm |
表2通过高锰酸盐介导的氧化证明碘载体产生
Claims (22)
1.一种产生碘载体的组合物,其包括碘化物/碘酸盐离子的来源,硫氰酸盐离子的来源和氧化剂,其为能够原位或非原位反应以产生碘载体的化合物。
2.根据权利要求1所述的组合物,其不包含有机稳定剂。
3.根据权利要求1或权利要求2所述的组合物,其中所述碘化物/碘酸盐离子的来源选自碘化钾、碘化钠、碘化锂、碘化铯、碘化氢、碘化铑、碘酸钾或碘酸钠。
4.根据前述权利要求中任一项所述的组合物,其中所述硫氰酸盐离子的来源选自硫氰酸钠、硫氰酸钾、硫氰酸锂、硫氰酸铯、硫氰酸、硫氰酸铑、烯丙基异硫氰酸盐、或氰酸盐化合物比如钾氰酸或硫化氰。
5.根据前述权利要求中任一项所述的组合物,其中所述氧化剂选自过氧化氢或高锰酸钾;过氧化钠;过氧化锂;释放过氧化物的过碳酸盐;释放过氧化物的柠檬酸或维生素C;过氧化物盐,其包括氧化钡、过硼酸钠、过氧化氢-尿素加合物;释放氧的假过氧化物,其包括超氧化物、二氧、臭氧、臭氧化物;有机过氧化物,其包括过氧酸、卤化酰基和脂肪族过氧化物。
6.根据前述权利要求中任一项所述的组合物,其中碘酸钾用作所述氧化剂和所述碘酸盐/碘离子来源二者。
7.根据前述权利要求中任一项所述的组合物,其中产生的所述碘载体是选自ISCN、I2SCN、I2(SCN)2、IOH(SCN)2、I3OH(SCN)2、I3OH(SCN)3、I4(SCN)4OH、I5(SCN)5的一种或多种碘-硫氰酸盐复合物。
8.根据前述权利要求中任一项所述的组合物,其中碘化物与硫氰酸盐的比值在0.1:10-10:1(按重量计)的范围中。
9.一种碘载体组合物,其包括当放置在水性环境中时根据前述权利要求中任一项所述的组合物的反应产物。
10.一种碘载体组合物,其包括至少一个氧、至少一个碘和至少一个硫化氰或氰酸单元。
11.根据前述权利要求中任一项所述的组合物,其进一步包括药学上有效的载体和稀释剂,优选地,其中所述药学上有效的载体是水、生理盐水、乳液、凝胶或水凝胶。
12.根据前述权利要求中任一项所述的组合物,其中所述组合物适合用于乳腺炎哺乳期反刍动物的治疗,
或适合于用作抗菌鼻冲洗剂,
或适合于用作抗菌漱口水,
或适合于用作抗菌洗液,
或适合于用作抗真菌洗液,
或适合于用作抗菌洗面奶/痤疮乳剂,
或适用于处理污染的牛奶或饲料、食品,
或适用于治疗由细菌、酵母菌、真菌、病毒、原生动物引起的感染,
或适合于材料、表面或环境的消毒,
或适合用于癌症的治疗。
13.根据前述权利要求中任一项所述的组合物,其适合于同时地或顺序地递送氧化剂与碘化物和硫氰酸盐组分。
14.根据前述权利要求中任一项所述的组合物,其适合于通过乳房内装置递送,或适合于通过浸湿的绷带递送。
15.根据前述权利要求中任一项所述的组合物,其中所述组合物被添加至绷带或泥罨剂,用于治疗创伤或烧伤感染。
16.根据前述权利要求中任一项所述的组合物,其中所述组合物以喷雾的形式被雾化,用于治疗人或动物的肺的细菌或真菌感染。
17.一种产生碘载体的方法,其包括在水性环境中混合碘化物离子的来源、硫氰酸盐离子的来源和氧化剂。
18.一种根据权利要求17所述的方法,其通过混合1%w/v硫氰酸钾(KSCN)、1%w/v碘化钾(KI)和1%w/v过氧化氢(H2O2)制备。
19.一种降低牛奶或饲料的细菌污染的方法,其包括施用根据权利要求1至16中任一项所述的组合物。
20.一种降低乳腺中的细菌接种量的方法,其包括施用根据权利要求1至16中任一项所述的组合物。
21.一种根据权利要求1至16中任一项所述的组合物,其适合于口服施用、静脉内施用、外用施用或肠胃外施用。
22.一种根据权利要求1至16中任一项所述的组合物,其被配制为乳剂、凝胶或糊剂。
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CN201911363345.2A Pending CN111642518A (zh) | 2014-08-20 | 2015-08-20 | 在有机材料存在下具有改善的稳定性的碘载体组合物 |
CN201580055477.2A Pending CN107072215A (zh) | 2014-08-20 | 2015-08-20 | 在有机材料存在下具有改善的稳定性的碘载体组合物 |
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CN201580055477.2A Pending CN107072215A (zh) | 2014-08-20 | 2015-08-20 | 在有机材料存在下具有改善的稳定性的碘载体组合物 |
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US (2) | US20170232038A1 (zh) |
EP (2) | EP2987408A1 (zh) |
JP (2) | JP2017534570A (zh) |
CN (2) | CN111642518A (zh) |
AU (1) | AU2015306137C1 (zh) |
BR (1) | BR112017003294A2 (zh) |
CA (1) | CA2958353A1 (zh) |
WO (1) | WO2016026946A1 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
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DE112008001301T5 (de) | 2007-05-14 | 2010-04-29 | Reserach Foundation Of State University Of New York | Induktion einer physiologischen Dispersions-Antwort in Bakterien-Zellen in einem Biofilm |
EP2987408A1 (en) * | 2014-08-20 | 2016-02-24 | National University of Ireland, Galway | Iodophor composition with improved stability in the presence of organic material |
FR3041269B1 (fr) | 2015-09-17 | 2020-04-17 | Taradon Laboratory | Composition comprenant des ions i2scn- et/ou des ions i(scn)2- |
CA3025115A1 (en) * | 2017-11-29 | 2019-05-29 | Eugene Joseph Pancheri | Method for desinfection of items and spaces |
US11541105B2 (en) | 2018-06-01 | 2023-01-03 | The Research Foundation For The State University Of New York | Compositions and methods for disrupting biofilm formation and maintenance |
GB201816558D0 (en) * | 2018-10-10 | 2018-11-28 | Slainte Beoga Teoranta | Antibiotic-free antimicrobial feed additives and antimicrobial compositions |
CN111632192B (zh) * | 2020-06-19 | 2021-09-24 | 浙江大学 | 兼具抗菌、促成骨分化及矿化的载碘钛合金植入物及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1098252A (zh) * | 1988-04-11 | 1995-02-08 | 埃培托普公司 | 储存稳定的固体碘前体杀菌组合物 |
WO2000001237A1 (en) * | 1998-07-06 | 2000-01-13 | Knoll Aktiengesellschaft | Sporicidal composition |
CN1889829A (zh) * | 2003-12-04 | 2007-01-03 | 巴斯福股份公司 | 包含聚合稳定剂的抗微生物组合物 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL70972A (en) * | 1983-03-02 | 1987-10-30 | Euro Celtique Sa | Method of producing standardized iodophor preparations and iodophor preparations produced thereby |
GB9002422D0 (en) * | 1990-02-03 | 1990-04-04 | Boots Co Plc | Anti-microbial compositions |
GB9406075D0 (en) * | 1994-03-26 | 1994-05-18 | Boots Co Plc | Method of killing microorganisms |
US5972355A (en) * | 1997-09-30 | 1999-10-26 | E-L Management Corp. | Stable compositions containing biologically active components |
ATE233050T1 (de) * | 1997-11-05 | 2003-03-15 | Koppert Bv | Bekämpfungsmittel gegen pflanzenpathogene mikro- organismen |
GB0100643D0 (en) * | 2001-01-10 | 2001-02-21 | Basf Ag | Liquid antimicrobial compositions |
US7709001B2 (en) * | 2005-04-08 | 2010-05-04 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
JP4892727B2 (ja) * | 2006-09-21 | 2012-03-07 | 国立大学法人 鹿児島大学 | 高分子タンニンの酵素的架橋反応 |
CA2933788C (en) * | 2008-09-03 | 2017-11-28 | Nbc Meshtec, Inc. | Antiviral agent |
EP2510944A1 (en) * | 2011-04-15 | 2012-10-17 | National University of Ireland, Galway | Treatment of bacterial infections |
CN103271091B (zh) * | 2013-05-17 | 2015-04-29 | 北京依科曼生物技术有限公司 | 一种含乳蛋白组合物的植物用杀菌剂 |
EP2987408A1 (en) * | 2014-08-20 | 2016-02-24 | National University of Ireland, Galway | Iodophor composition with improved stability in the presence of organic material |
-
2014
- 2014-08-20 EP EP14181684.3A patent/EP2987408A1/en not_active Withdrawn
-
2015
- 2015-08-20 EP EP15759685.9A patent/EP3193614A1/en not_active Withdrawn
- 2015-08-20 JP JP2017508607A patent/JP2017534570A/ja active Pending
- 2015-08-20 US US15/504,616 patent/US20170232038A1/en not_active Abandoned
- 2015-08-20 CN CN201911363345.2A patent/CN111642518A/zh active Pending
- 2015-08-20 BR BR112017003294A patent/BR112017003294A2/pt not_active IP Right Cessation
- 2015-08-20 CA CA2958353A patent/CA2958353A1/en not_active Abandoned
- 2015-08-20 AU AU2015306137A patent/AU2015306137C1/en not_active Ceased
- 2015-08-20 WO PCT/EP2015/069190 patent/WO2016026946A1/en active Application Filing
- 2015-08-20 CN CN201580055477.2A patent/CN107072215A/zh active Pending
-
2020
- 2020-07-01 JP JP2020114301A patent/JP2020183396A/ja active Pending
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2021
- 2021-02-16 US US17/176,782 patent/US20210236541A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1098252A (zh) * | 1988-04-11 | 1995-02-08 | 埃培托普公司 | 储存稳定的固体碘前体杀菌组合物 |
WO2000001237A1 (en) * | 1998-07-06 | 2000-01-13 | Knoll Aktiengesellschaft | Sporicidal composition |
CN1889829A (zh) * | 2003-12-04 | 2007-01-03 | 巴斯福股份公司 | 包含聚合稳定剂的抗微生物组合物 |
Non-Patent Citations (1)
Title |
---|
中国标准出版社第一编辑室: "《中国食品工业标准汇编 乳制品和婴幼儿食品卷》", 中国标准出版社, pages: 609 - 614 * |
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AU2015306137C1 (en) | 2019-05-23 |
US20170232038A1 (en) | 2017-08-17 |
AU2015306137A1 (en) | 2017-03-09 |
CN107072215A (zh) | 2017-08-18 |
AU2015306137B2 (en) | 2019-05-16 |
JP2017534570A (ja) | 2017-11-24 |
EP2987408A1 (en) | 2016-02-24 |
WO2016026946A1 (en) | 2016-02-25 |
JP2020183396A (ja) | 2020-11-12 |
US20210236541A1 (en) | 2021-08-05 |
CA2958353A1 (en) | 2016-02-25 |
BR112017003294A2 (pt) | 2018-07-03 |
EP3193614A1 (en) | 2017-07-26 |
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