CN101437504A - 含金属的杀病毒组合物及其用途 - Google Patents
含金属的杀病毒组合物及其用途 Download PDFInfo
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- CN101437504A CN101437504A CNA2007800087639A CN200780008763A CN101437504A CN 101437504 A CN101437504 A CN 101437504A CN A2007800087639 A CNA2007800087639 A CN A2007800087639A CN 200780008763 A CN200780008763 A CN 200780008763A CN 101437504 A CN101437504 A CN 101437504A
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- described compositions
- compositions
- copper
- zinc
- selenium
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- Pending
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Classifications
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- 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
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K33/02—Ammonia; Compounds thereof
-
- 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
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
-
- 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
- A61K33/32—Manganese; Compounds thereof
-
- 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
- A61K33/34—Copper; Compounds thereof
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Virology (AREA)
- Oncology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
一种用于治疗或预防呼吸道病毒的组合物,包括:(a)至少一种能在水溶液中解离为锌、铜、硒和/或锰离子的水溶性的锌、铜、硒和/或锰化合物;(b)至少一种能在水溶液中解离为铵离子的水溶性的铵试剂;(c)至少一种酸,和(d)水。
Description
本发明涉及杀病毒组合物及其在预防和/或治疗一系列病毒种属,特别是预防和/或治疗引起人或动物呼吸道疾病的病毒中的用途。这里使用的术语“治疗”和“处理”包括杀灭病毒或病毒的颗粒或控制/阻止病毒复制。更具体地,本发明的所有方面涉及用于治疗和/或预防普通感冒和/或流感和/或引起肺炎的病毒的组合物。甚至更具体地,本发明的所有方面涉及用于治疗和/或预防包括例如H1N1、H7N7、H9N2或H5N1病毒株在内的流感病毒株的组合物,后者导致高死亡率的禽流感。已知H5N1流感病毒株引起的感染,例如,对肺产生如后所述的有害和严重的影响。
禽流感(或其他H5N1病毒株)有传播到感染区域以外的趋势。病毒传播被限制在从感染的禽类传播给人类的同时,考虑到最近有限的证据人们担心通过病毒变异成可在不同动物种属间传播的形式,人与人之间传播。
由于禽“流感”与高死亡率有关,其变异到高感染性、可在人类之间传染的形式这一事件提高了人们对能产生真实灾难的“广泛流行”的后果的恐惧。同时,高度希望治疗和在可能时预防呼吸道病毒感染,特别需要提供能有效治疗和/或预防更严重的呼吸道病毒感染的制剂,包括例如H5N1呼吸道病毒株引起的最严重的此类感染。
与多数能被已知的常规抗菌药如抗生素治疗的细菌感染不同,呼吸道病毒感染,如普通感冒或流感,不能使用抗生素治疗。对大部分的呼吸道病毒感染来说,绝大多数现有的抗病毒药物是无效的,机体自身的免疫防御系统不得不对抗病毒感染。同时,这是普通感冒和流感的典型情况,特别是H5N1流感病毒株,H1N1和H7N7流感病毒株也是这种情况。
在相关的医学文献中,有很多关于H5N1病毒感染的作用模式和人体天然免疫防御系统抵御病毒的弱点的知识。然而,只提供了非常有限的治疗方法。一个能够用于禽流感的预防和/或感染后治疗的抗病毒药物是磷酸奥塞米韦,由罗氏以商品名达菲(TAMIFLU)上市销售。然而,该药品的供应有限;它的价格特别昂贵并且具有潜在的副作用。此外,在禽流感大面积流行期间储备了达菲(TamifluTM)的很多国家大量使用该药物时,人们担心病毒对达菲产生耐药性。达菲的活性代谢物非常稳定,它们在水中的累积会很快导致流感病毒的耐药性。
尽管有疫苗可以作为预防的手段对抗特定的有限的流感病毒株,目前市场上没有有效的疫苗能够作为预防手段对抗人类感染,如H5N1流感病毒株感染。H5N1病毒诱导产生一种促炎性的“细胞因子风暴”,它们是高耐药性的并对肺产生严重损伤,并危及了对抗病毒感染的免疫功能。这些因素单独使H5N1病毒株特别难以用大多数的现有抗病毒药物预防或治疗。
现在,我们惊奇的发现含有一种特定的窄范围的矿物质,或其他金属元素的如我们早期公开的专利WO01/15554中公开的作为宽范围的多功能产物的组合物,及其组合,在包括预防性处理H5N1病毒株感染的呼吸道病毒感染的治疗中具有意料不到的用途。我们还吃惊的发现这些选定的组合物,特别是这些金属离子的组合,可以被混合到新的凝胶剂或其他载体制剂中,并以喷雾剂或手部擦剂的形式使用以提供如下所示的以下本发明实施方式:
(i)作为预防性处理手段对呼吸道病毒,特别是流感病毒H5N1病毒株感染的预防起到支持作用的鼻喷雾剂和凝胶载体制剂;在优选的实施方式中,粘度小于4750厘泊,例如小于4500厘泊,优选小于4000厘泊,理想的是小于3000厘泊,例如在1-2500厘泊的范围内。
(ii)具有强大杀病毒能力的、用于控制(例如杀死、变为无害的或其他影响复制的)活病毒或病毒颗粒的清洁凝胶,和
(iii)手部擦剂,例如浸渍了组合物的可一次性使用的擦剂,并且可选择性的使用增稠剂或稳定剂来进行改良。
我们还提供了适宜的口服剂量形式的实施方式,例如,(iv)基于液体水性组合物的口服给药制剂。水性组合物可以具有选自特定范围的单一或多种金属离子。水性组合物可以全部由活性成分组成,或者也可以是主要由所述活性成分组成。在其他实施方式中,金属离子组合物可以包括可选的添加剂例如一种或多种赋形剂和/或稀释剂。
因此,本发明在一个方面提供了一种用于治疗呼吸道病毒的组合物,其含有:
(a)至少一种能在水溶液中解离为锌、铜、硒和/或锰离子的水溶性的锌、铜、硒和/或锰化合物;
(b)至少一种能在水溶液中解离为铵离子的水溶性的铵试剂;
(c)至少一种酸,和
(d)水
所述组合物优选具有小于4的pH值,并且优选电势超过50毫伏。
本发明在另一个方面提供了一种如上述定义的、用于治疗流感病毒的组合物,例如流感病毒H1N1、H7N7、H9N2或H5N1病毒株,优选H5N1病毒株。
本发明的又一个方面提供了一种如上述定义的、用于治疗引起普通感冒症状的病毒的组合物。
本发明进一步的一个方面提供了一种如上述定义的组合物在制备用于治疗呼吸道病毒,如流感病毒,优选流感病毒H5N1病毒株,或者普通感冒病毒或肺炎病毒感染的药物中的用途。60%的普通感冒由鼻病毒引起。其他由冠状病毒、流感病毒、副流感病毒、呼吸合胞病毒、腺病毒和肠道病毒引起。此外,肺炎支原体和肺炎衣原体也可能引起普通感冒症状。
上述定义的组合物可以含有一种或多种选自维生素B1、B、B5、B6、C、苹果酸、天然利尿剂、褪黑激素和缬草属植物镇静剂的添加剂。所述组合物可以基本上或优选全部由所述成分组成。最优选所述的水是蒸馏水。
优选锌、铜、硒和/或锰化合物是其无机盐,例如磷酸盐、硫酸盐、硝酸盐或盐酸盐。
能够结合、复合或另外掩蔽锌、铜和/或硒离子的铵试剂是能够方便的在水溶液中解离成铵离子的无机铵盐或氢氧化铵。例如,一种或多种以下物质可以出现在组合物中:氢氧化铵、硫酸铵、氯化铵、磷酸铵、硝酸铵、柠檬酸铵和酒石酸铵。
所述至少一种酸方便的选自下组:硫酸、盐酸、硝酸、磷酸、柠檬酸和酒石酸。例如,所述至少一种酸可以是浓的硫酸、盐酸、硝酸或磷酸。
组合物的pH可以小于4,例如3.5或更低,3或更低,2.5或更低,例如2或更低例如在1或更小的范围内。电势可以是例如超过100毫伏,或超过150毫伏,或超过200毫伏,或超过250毫伏,或超过300毫伏,或超过340毫伏例如在高至400毫伏的范围内。
本发明包括的组合物可以通过我们早期公开的专利的“一般方法”部分描述的方法制备,象其中举例说明的那样,示例的表格中的金属或其他矿物元素至少是铜、锌、硒和锰中的一种。当使用含有多于一种金属离子的组合物时,铜和锌可以与或不与硒共存;硒和锌可以共同使用,与或不与铜共同使用。铜和硒可以共存,与或不与锌共同使用。所有都可以与锰共同使用,或者锰单独使用。适合的锰制剂可以由上述描述的一般方法外推的方法制备,使用例如硫酸锰、硫酸和硫酸铵来制得pH值为2或更小、电势超过250毫伏的组合物。
本发明进一步提供了如上述定义的对包括季节性流感、H5N1或禽流感、急性鼻炎在内的呼吸道感染有抗病毒活性的抗病毒组合物。这样的组合物可以包括一种或多种传统的药学可接受的载体、稀释剂和/或赋形剂,例如作为稀释剂的盐水。
为了例举本发明,下列完全但非限制性的、记载在我们早期公开的专利WO01/015554中的实施例用于制备合适的组合物。它们可以根据我们早期公开的所述专利中描述的相同一般方法制备。在下面的表1中,本发明的下列实施例与标明的在前实施例的编号相对应。
表1
实施例标号(本发明) | 实施例标号(早期的专利公开) | 出现的离子种类 |
1 | 1 | Cu2+,(NH4)+ |
2 | 2 | Cu2+,(NH4)+ |
3 | 3 | Cu2+,(NH4)+ |
4 | 4 | Cu2+,(NH4)+ |
5 | 11 | Se2+,(NH4)+ |
6 | 12 | Se2+,(NH4)+ |
7 | 15 | Zn2+,(NH4)+ |
8 | 16 | Zn2+,(NH4)+ |
9 | 17 | Zn2+,(NH4)+ |
10 | 18 | Zn2+,(NH4)+ |
11 | 18a | Zn2+,(NH4)+ |
12 | 19 | Cu2+,(NH4)+ |
13 | 20 | Cu2+,(NH4)+ |
14 | 21 | Cu2+,(NH4)+ |
15 | 22 | Cu2+,(NH4)+ |
16 | 23 | Zn2+,(NH4)+ |
17 | 24 | Cu2+,(NH4)+ |
18 | 25 | Cu2+,(NH4)+ |
19 | 26 | Cu2+,(NH4)+ |
20 | 27 | Cu2+,(NH4)+ |
21 | 29 | Cu2+,(NH4)+ |
22 | 30 | Cu2+,(NH4)+ |
23 | 31 | Cu2+,(NH4)+ |
24 | 32 | Cu2+,(NH4)+ |
25 | 33 | Cu2+,(NH4)+ |
26 | 34 | Cu2+,(NH4)+ |
27 | 35 | Cu2+,(NH4)+ |
28 | 36 | Cu2+,(NH4)+ |
29 | 37 | Cu2+,(NH4)+ |
30 | 38 | Cu2+,(NH4)+ |
31 | 43 | Zn2+,(NH4)+ |
32 | 45 | Zn2+,(NH4)+ |
如上述定义和示例的组合物可以以至少3种治疗方案来对抗呼吸道,特别是流感,更特别的是H5N1流感病毒。它们可以作为预防性处理来阻止病毒侵入鼻粘膜[通常最常见的侵入部位]和/或杀死病毒或病毒颗粒。这样的阻止通过使用鼻凝胶或水性喷雾剂,即含至少一种如上述定义和/或示例的组合物的药学可接受的凝胶或喷雾剂载体介质来实现。当病毒出现时,其可被抗感染凝胶制剂如净手凝胶控制,即,将组合物加入本身已知的局部用载体基质中,实质上是通过混合两种已知实体来得到新的抗病毒凝胶或喷雾制剂。此外,浸渍或包衣了组合物的一次性使用的擦手物质可以选择性的进行改造以提高其粘附性。优选使用至少含铜的组合物在鼻凝胶、清洁凝胶和擦手物质的方式来作为阻止病毒侵入和/或杀死或控制病毒或病毒颗粒的手段。
为证明本发明组合物的抗呼吸道病毒活性,制备了一些组合物并在体外和体内检测其抗H5N1流感病毒的活性以显示其管理禽流感的能力。含硒组合物的抗氧化性质直接指示了其杀病毒活性的潜力。列出了涉及只含锌、铜和硒的组合物的三个主要的实施方式,第四个实施方式涉及依次使用锰、锌和硒金属离子组合物:
1)鼠科动物体外抗人H5N1病毒活性研究(锌,铜和硒)
2)小鼠毒理学和剂量范围研究(锌)
3)对感染了致命性H5N1流感病毒的小鼠的预防活性(锌)和
4)人病例研究,其中依次内服给药锰、锌和硒组合物联合疗法缓解传统流感病毒感染。
实施例1
体外对人H5N1的杀病毒活性研究
在体外杀病毒实验中,A/Vietnam/1203/04(H5N1)x AnnArbor/6/60流感病毒与铜金属离子组合物(相当于铜元素3ppm),锌金属离子组合物(相当于锌元素2ppm)和硒金属离子组合物(相当于硒元素1ppm)或水(对照)在室温下作用10分钟。然后使用标准MDCK细胞分析法测定处理过的病毒的感染性。
下面表2中的结果表明,尽管锌和硒组合物在它们异常低的浓度下未显示明显直接的抗病毒作用,铜组合物尽管在类似的异常低浓度下却引起了病毒计数大于90%的减少。
表2
样品 | 浓度(ppm)相对于酸度/pH值的初始低剂量 | 病毒计数减少值的Log 10 |
铜 | 3 | 1.75+/-0.00** |
锌 | 2 | 0.25+/-0.35 |
硒 | 1 | 0.88+/-0.88 |
水 | N/A | 0.00+/-0.00 |
**与水有显著性差异(p<0.001)
这些结果表明含有至少3ppm(=3μg/ml)离子修饰铜的组合物的鼻凝胶可以不仅提供了阻止病毒侵入上呼吸道的屏障,而且可能还杀死了大部分接触到凝胶的病毒颗粒。由于流感病毒可以从感染的表面脱离并在侵入时向鼻子和眼睛的部位转移,使用含有至少3ppm铜组合物的擦手物质或手用凝胶作为预防手段对减少或预防感染,特别是大面积流行具有实质性的益处。
实施例2
小鼠毒理学和剂量范围研究
初步进行了小鼠体内毒理学/剂量范围研究以便在开始预防研究前确定锌金属离子组合物在不同剂量水平的安全性。3只小鼠的组以以下剂量每天一次,口服,共14天接受锌制剂,(i)四倍人推荐每日允许剂量(人的RDA是每天15mg锌元素)(ii)十二倍人RDA(相当于1倍小鼠RDA)和(iii)三十六倍人RDA。
小鼠在治疗开始前(和最后一次治疗结束后18小时)称重,在给药期间观察毒性征候。没有毒性征候被记录下来。在给药期结束后进行了小鼠体内器官的全面检查,未观察到明显的异常。
实施例3
对感染了致命性H5N1流感病毒,即适用于小鼠的流感病毒A/鸭/MN/1525/81(H5N1)的小鼠的预防活性。
为进行预防活性研究,10只雌性BALB/c小鼠的组(6-8周大,体重大约20g)以1倍和36倍人RDA(相当于1/12和3倍小鼠RDA)的剂量口服接受以蒸馏水稀释的锌金属离子组合物,持续给药3天,每天2次给药,即上午和下午各给药1次。安慰剂组(20只小鼠)每天2次给予蒸馏水。
最后一次给药后四小时,给小鼠鼻内接种前述的致命性H5N1病毒。持续每天两次给药直到研究结束(21天或小鼠死亡)。
另一组10只小鼠在鼻内接种病毒后四小时,以10mg/kg的剂量每天两次口服给药达菲(TamifluTM)(磷酸奥塞米韦),持续5天。每天测定血氧水平(提供肺功能的衡量指标),在研究开始和结束时给小鼠称重。
截至第19天的结果总结于下面的表3A中,全部结果列于表3中。
表3A
治疗 | 给药剂量(mg/kg) | 第19天每组存活小鼠数 |
锌 | 8.74(3倍人RDA) | 8/10[80%] |
锌 | 0.24(1/12人RDA) | 5/10[50%] |
水/对照 | Ni1 | 8/20[40%] |
达菲 | 10 | 10/10[100%] |
实施例4:流感-人感染案例研究
关键词ZnAL42≡实施例7,SePC33≡实施例5MnAL42=根据前述方法制备的含可溶性锰化合物的锰金属离子制剂
在四个不同的场合发现,一个深受呼吸道病毒感染之苦的哮喘病人,在感冒或流感开始时(以典型感冒和流感的前驱症状和哮喘确定)以RDA的剂量,每天3次,共3-4天联合服用ZnAL42,MnAL42和SePC33能彻底阻止感冒和流感的发展。没有联合使用金属离子制剂的此个体通常需要4-6天的卧床休息,并通常发展成进一步恶化为呼吸困难的胸部感染,使患病时间延长到2周。
一些其他非哮喘的、有规律使用ZnAL42产品的病人发现,当感冒或流感的症状开始出现时,增大ZnAL42的剂量到3倍RDA可以将感染期缩短2到5天。
Johnston的研究小组报告,感染鼻病毒的哮喘病人的支气管上皮细胞产生的β和λ干扰素比非哮喘病人的少。因此,假定并未受理论束缚的是,ZnAL42或联合使用ZnAL42,MnAL42和SePC33能增强抗病毒干扰素的产生,因此改善了病毒感染及其在肺部的致病效果。
这里现在提供了含铜金属离子组合物的凝胶基质组合物的实施例。
实施例33(凝胶基组合物)
表5
制备方法
步骤1.将B相加入A相,混合均匀
N.B.芦荟凝胶基质优选通过以下方法制备:水解200:1的翠绿芦荟片,以0.5%黄原胶增稠,澄清后加入0.1%山梨酸钾和0.1%苯甲酸钠。
*注释:见后面的实施例34
实施例34(改进的凝胶基组合物)
表6
制备方法
步骤1.在A相的水中缓慢溶解芦荟片
步骤2.加热A相到38-40℃
步骤3.将黄原胶缓慢加入涡旋震荡的水相中。用45分钟使黄原胶彻底溶解。
步骤4.加入预先溶解的山梨酸钾和苯甲酸钠—C相—至凝胶混合物。混合均匀。
步骤5.加入D相—CU AL 42—混合均匀
*注释:与水溶性制剂相比,明显过量的铜金属离子组合物被加入凝胶制剂中。尽管浓度较高,当应用于例如鼻腔时,芦荟基质能够掩饰不希望有的金属余味。
Claims (24)
1.一种用于治疗或预防呼吸道病毒的组合物,其含有:
(a)至少一种能在水溶液中解离为锌、铜、硒和/或锰离子的水溶性的锌、铜、硒和/或锰化合物;
(b)至少一种能在水溶液中解离为铵离子的水溶性的铵试剂;
(c)至少一种酸,和
(d)水。
2.一种用于治疗或预防呼吸道病毒的组合物,主要由以下物质组成:
(a)至少一种能在水溶液中解离为锌、铜、硒和/或锰离子的水溶性的锌、铜、硒和/或锰化合物;
(b)至少一种能在水溶液中解离为铵离子的水溶性的铵试剂;
(c)至少一种酸,和
(d)水。
3.一种用于制备用于治疗或预防呼吸道病毒的药物的组合物,该组合物含有:
(a)至少一种能在水溶液中解离为锌、铜、硒和/或锰离子的水溶性的锌、铜、硒和/或锰化合物;
(b)至少一种能在水溶液中解离为铵离子的水溶性的铵试剂;
(c)至少一种酸,和
(d)水。
4.一种用于制备用于治疗或预防呼吸道病毒的药物的组合物,该组合物主要由以下物质组成:
(a)至少一种能在水溶液中解离为锌、铜、硒和/或锰离子的水溶性的锌、铜、硒和/或锰化合物;
(b)至少一种能在水溶液中解离为铵离子的水溶性的铵试剂;
(c)至少一种酸,和
(d)水。
5.前述任意一项权利要求所述的组合物,其具有的pH值小于4。
6.前述任意一项权利要求所述的组合物,其具有的电势超过50毫伏。
7.前述任意一项权利要求所述的组合物,其进一步包括赋形剂或稀释剂。
8.权利要求7所述的组合物,其中所述稀释剂包括盐水。
9.前述任意一项权利要求所述的组合物,其是抗病毒凝胶的形式。
10.权利要求1-8任意一项所述的组合物,其是喷雾剂的形式,例如适合鼻用的喷雾剂。
11.权利要求1-8任意一项所述的组合物,其是用组合物浸渍的物质的形式。
12.前述任意一项权利要求所述的组合物,其中治疗或预防的病毒是流感病毒。
13.权利要求12所述的组合物,其中所述病毒是H1N1、H7N7、H9N2或H5N1病毒株。
14.前述任意一项权利要求所述的组合物,其中所述病毒株是H5N1并且与引起禽流感有关。
15.权利要求1-11任意一项所述的组合物,其中治疗或预防的病毒是引起普通感冒症状的呼吸道病毒。
16.根据权利要求1-11任意一项所述的组合物,其与另一种抗病毒制剂合用。
17.权利要求16所述的组合物,其中其他制剂是磷酸奥塞米韦。
18.前述任意一项权利要求所述的组合物,其中至少存在两种不同的所述金属离子。
19.权利要求18所述的组合物,其中锌金属离子与铜、硒和锰金属离子中的一种或多种同时出现。
20.权利要求9-19任意一项所述的组合物,其中所述凝胶以翠绿芦荟为基质。
21.权利要求20所述的组合物,其中所述凝胶含有至少一种增稠剂,例如黄原胶。
22.权利要求21所述的组合物,其中至少存在一种防腐剂。
23.权利要求9或20-22任意一项所述的组合物,其中所述凝胶含有铜金属离子。
24.权利要求23所述的组合物,其中所述凝胶中存在的铜离子的量在100-500ppm范围内,优选150-450ppm,更优选200-350ppm。
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GBGB0602325.3A GB0602325D0 (en) | 2006-02-06 | 2006-02-06 | Virucidal compositions and uses |
GB0602325.3 | 2006-02-06 |
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CN101437504A true CN101437504A (zh) | 2009-05-20 |
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CNA2007800087639A Pending CN101437504A (zh) | 2006-02-06 | 2007-02-06 | 含金属的杀病毒组合物及其用途 |
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US (1) | US20090304813A1 (zh) |
JP (1) | JP2009526029A (zh) |
CN (1) | CN101437504A (zh) |
AU (1) | AU2007213569A1 (zh) |
BR (1) | BRPI0707697A2 (zh) |
CA (1) | CA2641502A1 (zh) |
GB (2) | GB0602325D0 (zh) |
IL (1) | IL193273A0 (zh) |
MX (1) | MX2008010155A (zh) |
RU (1) | RU2008135945A (zh) |
WO (1) | WO2007091037A2 (zh) |
ZA (1) | ZA200807665B (zh) |
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WO2011041938A1 (zh) * | 2009-10-08 | 2011-04-14 | 富莱生物技术投资有限公司 | 一种以苯甲酸和有机酸防腐剂相联合作为有效成分的组合物及其用途 |
WO2018064978A1 (zh) * | 2016-10-09 | 2018-04-12 | 曾忠铭 | 一种抑菌剂配伍在制备阴道用组合物中的用途与阴道用组合物 |
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Publication number | Priority date | Publication date | Assignee | Title |
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GB0612917D0 (en) * | 2006-06-29 | 2006-08-09 | Remedy Res Ltd | Metallic compositions,preparations and uses |
GB201211691D0 (en) | 2012-07-05 | 2012-08-15 | Reckitt Benckiser Llc | Sprayable aqueous alcoholic microbicidal compositions comprising zinc ions |
GB201211702D0 (en) | 2012-07-02 | 2012-08-15 | Reckitt Benckiser Llc | Sprayable aqueous alcoholic microbicidal compostions comprising zinc ions |
GB201211701D0 (en) | 2012-07-02 | 2012-08-15 | Reckitt Benckiser Llc | Aqueous alcoholic microbicidal compositions comprising zinc ions |
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Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5997911A (en) * | 1996-08-27 | 1999-12-07 | Brinton Veterinary Supply, Inc. | Composition and method for reducing diarrhea in poultry and swine |
KR20010013377A (ko) * | 1997-06-04 | 2001-02-26 | 데이비드 엠 모이어 | 마일드한 잔류성 항균 조성물 |
NZ530193A (en) * | 1999-08-31 | 2005-08-26 | Remedy Res Ltd | Metal-containing compositions, preparations and uses |
US20040033260A1 (en) * | 1999-10-19 | 2004-02-19 | The Procter & Gamble Company | Compositions for prevention and treatment of cold and influenza-like symptoms comprising chelated zinc |
US7166435B2 (en) * | 2001-08-06 | 2007-01-23 | The Quigley Corporation | Compositions and methods for reducing the transmissivity of illnesses |
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MX2008006507A (es) * | 2005-11-17 | 2008-11-27 | Remedy Res Ltd | Productos para el control de patogenos. |
US20080045482A1 (en) * | 2006-01-27 | 2008-02-21 | Adventrx Pharmaceuticals, Inc. | Compositions and methods for the treatment of viral infections |
-
2006
- 2006-02-06 GB GBGB0602325.3A patent/GB0602325D0/en not_active Ceased
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2007
- 2007-02-06 MX MX2008010155A patent/MX2008010155A/es unknown
- 2007-02-06 US US12/278,383 patent/US20090304813A1/en not_active Abandoned
- 2007-02-06 AU AU2007213569A patent/AU2007213569A1/en not_active Abandoned
- 2007-02-06 BR BRPI0707697-5A patent/BRPI0707697A2/pt not_active IP Right Cessation
- 2007-02-06 JP JP2008553819A patent/JP2009526029A/ja active Pending
- 2007-02-06 CA CA002641502A patent/CA2641502A1/en not_active Abandoned
- 2007-02-06 GB GB0816431A patent/GB2453826A/en not_active Withdrawn
- 2007-02-06 RU RU2008135945/15A patent/RU2008135945A/ru not_active Application Discontinuation
- 2007-02-06 CN CNA2007800087639A patent/CN101437504A/zh active Pending
- 2007-02-06 WO PCT/GB2007/000394 patent/WO2007091037A2/en active Application Filing
-
2008
- 2008-08-06 IL IL193273A patent/IL193273A0/en unknown
- 2008-09-05 ZA ZA200807665A patent/ZA200807665B/xx unknown
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WO2011041938A1 (zh) * | 2009-10-08 | 2011-04-14 | 富莱生物技术投资有限公司 | 一种以苯甲酸和有机酸防腐剂相联合作为有效成分的组合物及其用途 |
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WO2018064978A1 (zh) * | 2016-10-09 | 2018-04-12 | 曾忠铭 | 一种抑菌剂配伍在制备阴道用组合物中的用途与阴道用组合物 |
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Also Published As
Publication number | Publication date |
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WO2007091037A3 (en) | 2009-02-12 |
RU2008135945A (ru) | 2010-03-20 |
MX2008010155A (es) | 2008-10-17 |
GB2453826A (en) | 2009-04-22 |
GB0816431D0 (en) | 2008-10-15 |
JP2009526029A (ja) | 2009-07-16 |
CA2641502A1 (en) | 2007-08-16 |
ZA200807665B (en) | 2009-10-28 |
IL193273A0 (en) | 2009-08-03 |
BRPI0707697A2 (pt) | 2011-05-10 |
AU2007213569A1 (en) | 2007-08-16 |
US20090304813A1 (en) | 2009-12-10 |
WO2007091037A2 (en) | 2007-08-16 |
GB0602325D0 (en) | 2006-03-15 |
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