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HK40091974A - Solid composition for producing antibacterial, antiviral, antifungal and disinfectant solutions - Google Patents

Solid composition for producing antibacterial, antiviral, antifungal and disinfectant solutions Download PDF

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Publication number
HK40091974A
HK40091974A HK62023079234.8A HK62023079234A HK40091974A HK 40091974 A HK40091974 A HK 40091974A HK 62023079234 A HK62023079234 A HK 62023079234A HK 40091974 A HK40091974 A HK 40091974A
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solid composition
water
optionally
sodium
inert filler
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HK62023079234.8A
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Chinese (zh)
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理查德·斯特德
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库尔集团有限公司
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Description

用于生产抗菌、抗病毒、抗真菌和杀菌溶液的固体组合物Solid compositions used to produce antibacterial, antiviral, antifungal, and bactericidal solutions.

技术领域Technical Field

本发明涉及一种固体组合物,其可被添加至水性体系中以生产抗菌、抗病毒、抗真菌和杀菌溶液。This invention relates to a solid composition that can be added to an aqueous system to produce antibacterial, antiviral, antifungal, and bactericidal solutions.

背景技术Background Technology

酶和酶体系是本领域熟知的天然抗菌剂。这些酶和酶体系中的实例是天然生成的过氧化物酶体系,其具有抗菌性质。然而,过氧化物酶本身并不具有抗菌作用。完整的抗菌过氧化物酶体系需要如下三种成分:过氧化物酶酶催化剂,过氧化氢和诸如带负电荷的卤素或拟卤素之类的可氧化的底物。过氧化物酶催化的(拟)卤素的氧化产生氧化微生物的反应试剂,其会破坏微生物的必要的结构和功能成分,从而抑制微生物代谢和生长。Enzymes and enzyme systems are well-known natural antimicrobial agents. An example of such enzymes and enzyme systems is the naturally occurring peroxidase system, which possesses antimicrobial properties. However, peroxidases themselves do not have antimicrobial activity. A complete antimicrobial peroxidase system requires three components: a peroxidase catalyst, hydrogen peroxide, and an oxidizable substrate such as a negatively charged halogen or pseudohalogen. The peroxidase-catalyzed oxidation of the (pseudo)halogen produces a reaction agent that oxidizes microorganisms, destroying essential structural and functional components of the microorganisms, thereby inhibiting their metabolism and growth.

不同的过氧化物酶优先氧化不同的卤素或(拟)卤素,产生不同的抗菌物种。例如,中性粒细胞的髓过氧物酶(MPO)使用氯化物作为底物并且形成次氯酸作为主产物。奶产品中的乳过氧化物酶(LPO)和唾液中的唾液过氧化物酶(SPO)易于氧化硫氰酸盐(SCN-)并产生次硫氰酸或其共轭碱次硫氰酸盐(OSCN-),后者是大多数生理溶液中的主要成分。碘化物(I-)也可被MPO,LPO和SPO氧化,并且,在体外,碘化物是所有卤化物中最容易被氧化的。Different peroxidases preferentially oxidize different halogens or (pseudo)halogens, producing different antimicrobial species. For example, myeloperoxidase (MPO) in neutrophils uses chloride as a substrate and forms hypochlorous acid as the main product. Lactoperoxidase (LPO) in dairy products and salivary peroxidase (SPO) in saliva readily oxidize thiocyanate (SCN-) to produce hypothiocyanate or its conjugate base hypothiocyanate (OSCN-), the latter being the main component in most physiological solutions. Iodide (I-) can also be oxidized by MPO, LPO, and SPO, and in vitro, iodide is the most readily oxidized of all halides.

这些过氧化物酶体系(以及从植物衍生而来的这些过氧化物酶体系)是本领域熟知的并且在生产抗菌、抗病毒、抗真菌和杀菌的溶液方面非常理想。然而,这些过氧化物酶体系的使用通常会由于这些体系中所涉及的化学物质的化学稳定性而受到限制并且通常不太可能长时间的储存这些过氧化物酶体系。这些基于过氧化物酶的产品通常会遇到如下问题:These peroxidase systems (and those derived from plants) are well known in the art and are ideal for producing antibacterial, antiviral, antifungal, and bactericidal solutions. However, the use of these peroxidase systems is often limited by the chemical stability of the chemicals involved and is generally not suitable for long-term storage. These peroxidase-based products typically encounter the following problems:

·储存期短Short shelf life

·含有活性物质的溶液的半衰期短Solutions containing active substances have short half-lives.

·难于制备Difficult to prepare

·产物中需要促凝剂(通常是金属盐)以稳定和/或分离水中的悬浮物。如果使用这样的产品接触食物,那么这些促凝剂(例如,基于铝的促凝剂)是非常不理想的·制备这些产品的生产成本通常非常高• The product requires a coagulant (usually a metal salt) to stabilize and/or separate suspended solids in the water. These coagulants (e.g., aluminum-based coagulants) are highly undesirable if the product is intended for food contact. • The production cost of these products is typically very high.

鉴于上述原因设计了本发明。The present invention was designed for the reasons mentioned above.

发明内容Summary of the Invention

本发明提供一种固体组合物,其包含:This invention provides a solid composition comprising:

(a)固定的或非固定的过氧化物酶酶催化剂;(a) Fixed or non-fixed peroxidase catalyst;

(b)可氧化的底物,其选自:(b) Oxidizable substrates selected from:

(i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or

(ii)拟卤素及其衍生物;(ii) pseudohalogens and their derivatives;

(c)至少一种氧化剂;(c) at least one oxidizing agent;

(d)任选地,至少一种惰性填充物;以及(d) Optionally, at least one inert filler; and

(e)任选地,缓冲体系。(e) Optional, buffer system.

在另一方面,本发明提供一种试剂盒,其包含:In another aspect, the present invention provides a kit comprising:

第一固体组合物,其包含:A first solid composition comprising:

(a)过氧化物酶酶催化剂;(a) Peroxidase enzyme catalyst;

(b)可氧化的底物,其选自:(b) Oxidizable substrates selected from:

(i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or

(ii)拟卤素及其衍生物,以及(ii) pseudohalogens and their derivatives, and

(c)任选地,至少一种惰性填充物;(c) Optionally, at least one inert filler;

(d)任选地,缓冲体系,以及(d) Optionally, the buffer system, and

第二固体组合物,其包含:The second solid composition comprises:

(a)至少一种氧化剂,和(a) at least one oxidizing agent, and

(b)任选地,至少一种惰性填充物。(b) Optionally, at least one inert filler.

在本发明的另一方面,本发明提供一种试剂盒,其包含:In another aspect, the present invention provides a kit comprising:

第一固体组合物,其包含:A first solid composition comprising:

(a)过氧化物酶酶催化剂;(a) Peroxidase enzyme catalyst;

(b)任选地,至少一种惰性填充物,(b) Optionally, at least one inert filler,

第二固体组合物,其包含:The second solid composition comprises:

(c)可氧化的底物,其选自:(c) Oxidizable substrates selected from:

(i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or

(ii)拟卤素及其衍生物;(ii) pseudohalogens and their derivatives;

(d)任选地,至少一种惰性填充物,(d) Optionally, at least one inert filler.

(e)任选地,缓冲体系,以及(e) Optionally, the buffer system, and

第三固体组合物,其包含:The third solid composition comprises:

(a)至少一种氧化剂,和(a) at least one oxidizing agent, and

(b)任选地,至少一种惰性填充物。(b) Optionally, at least one inert filler.

在本发明的另一方面,本发明提供一种水性体系,其包含本文所述的固体组合物和水。在本发明的进一步的方面,所述水性体系用作抗菌溶液,杀菌,抗真菌和抗病毒溶液。所述水性体系可在对包括表面在内的材料进行清洁、洗涤和杀菌的方法中使用。In another aspect of the invention, an aqueous system is provided comprising the solid composition described herein and water. In a further aspect of the invention, the aqueous system is used as an antibacterial solution, a bactericide, an antifungal, and an antiviral solution. The aqueous system can be used in methods for cleaning, washing, and sterilizing materials, including surfaces.

所述水性体系可用于制备将会用于食品、药品和化妆品的溶液。此外,所述水性体系可用于喷洒至空气中并喷洒于各种表面以杀灭致病菌。例如,所述水性溶液可喷洒在封闭的空间内或限定的开放区域,例如,医院内的病房,等候区,临床环境以及飞机内部或易变质的物品的储存区域内以杀灭空气中传播的致病菌和表面上的致病菌。The aqueous system can be used to prepare solutions for use in food, pharmaceuticals, and cosmetics. Furthermore, the aqueous system can be sprayed into the air and onto various surfaces to kill pathogens. For example, the aqueous solution can be sprayed in enclosed spaces or defined open areas, such as hospital wards, waiting areas, clinical environments, and the interior of aircraft or storage areas for perishable goods, to kill airborne and surface pathogens.

在本发明的另一方面,本发明提供一种消毒水的方法,其包括如下步骤:In another aspect, the present invention provides a method for disinfecting water, comprising the following steps:

(i)将本文所述的固体组合物添加至待消毒的水中,或(i) Add the solid composition described herein to the water to be disinfected, or

(ii)使用本文所述的试剂盒,其中,将所述第一固体组合物和所述第二固体组合物添加至待消毒的水中,或(ii) Using the kit described herein, wherein the first solid composition and the second solid composition are added to the water to be disinfected, or

(iii)将所述水性体系添加至待消毒的水中。(iii) Add the aqueous system to the water to be disinfected.

在本发明的另一方面,本发明提供一种制备抗菌溶液、杀菌、抗真菌溶液和抗病毒溶液的方法,其包括如下步骤:In another aspect, the present invention provides a method for preparing antibacterial solutions, bactericidal, antifungal, and antiviral solutions, comprising the following steps:

(i)将本文所述的固体组合物添加至水中,或(i) Adding the solid composition described herein to water, or

(ii)使用本文所述的试剂盒,其中,将所述第一固体组合物和所述第二固体组合物添加至水中,(ii) Using the kit described herein, wherein the first solid composition and the second solid composition are added to water,

任选地,还添加其他抗感染试剂、抗菌剂、抗病毒剂、抗生素、抗真菌剂、防腐剂或杀菌剂。Optionally, other anti-infective agents, antibacterial agents, antiviral agents, antibiotics, antifungal agents, preservatives, or bactericides may also be added.

本发明包括上文所述的各个方面和优选的特征的组合,除非这样的组合明显是不可能的或明确被避免的。This invention includes combinations of the aspects and preferred features described above, unless such combinations are obviously impossible or explicitly avoided.

具体实施方式Detailed Implementation

本发明的各个方面和各个实施方式将参考附图在下文进行讨论。Various aspects and embodiments of the present invention will be discussed below with reference to the accompanying drawings.

图1显示了5升放大实验,其显示了在120小时的储存过程中所存在的次硫氰酸盐离子的量。Figure 1 shows a 5-liter scale-up experiment, illustrating the amount of hypothiocyanate ions present during 120 hours of storage.

图2显示了在24小时的储存过程中在使用了过氧化钙和过碳酸钠的条件下存在的次硫氰酸盐离子的量。Figure 2 shows the amount of hypothiocyanate ions present during 24 hours of storage under conditions using calcium peroxide and sodium percarbonate.

图3显示了在24小时的储存过程中相对于使用过氧化钙(未缓冲)和过碳酸钠(未缓冲),在使用过氧化钙(柠檬酸缓冲:柠檬酸三钠缓冲溶液缓冲)的条件下存在的次硫氰酸盐离子的量。Figure 3 shows the amount of hypothiocyanate ions present under the condition of using calcium peroxide (citric acid buffer: trisodium citrate buffer solution) relative to the use of calcium peroxide (unbuffered) and sodium percarbonate (unbuffered) during 24 hours of storage.

图4显示了在最后15分钟混合反应过程(添加过氧化钙/过碳酸钠之后)中ppm的变化。Figure 4 shows the change in ppm during the last 15 minutes of the mixing reaction process (after the addition of calcium peroxide/sodium percarbonate).

图5显示了混合过程中的pH变化。Figure 5 shows the pH changes during the mixing process.

根据本发明的组合物是固体形式。由此,在本文中,形成组合物的各个组分是指固体的并且优选地是干燥的。The composition according to the invention is in solid form. Therefore, in this document, the individual components forming the composition refer to solids and preferably dry ones.

在本文中,过氧化物酶酶催化剂是在自然界中广泛存在的游离酶。它们的主要作用是催化氧化反应,同时消耗诸如过氧化氢之类的氧化剂。为了使氧化反应进行下去,通常需要电子供体(还原剂)。In this paper, peroxidases are enzyme catalysts that are widely distributed free enzymes in nature. Their main function is to catalyze oxidation reactions while consuming oxidants such as hydrogen peroxide. An electron donor (reducing agent) is usually required for the oxidation reaction to proceed.

可在本发明中使用的过氧化物酶包括来自植物来源的过氧化物酶,包括但不限于:抗坏血酸盐过氧化物酶和基于硫醇的过氧化物酶。过氧化物酶也可以是来自于动物来源的或人来源的,包括但不限于:乳过氧化物酶,甲状腺过氧化物酶,髓过氧化物酶,嗜酸性粒细胞过氧化物酶和脲过氧化物酶。Peroxidases that can be used in this invention include plant-derived peroxidases, including but not limited to ascorbate peroxidase and thiol-based peroxidases. Peroxidases can also be of animal or human origin, including but not limited to lactoperoxidase, thyroid peroxidase, myeloperoxidase, eosinophil peroxidase, and urea peroxidase.

过氧化氢中存在的过氧化物酶和卤化物或硫氰酸盐中存在的过氧化物酶作为电子供体可产生具有多种不同的抗菌性能的产物。过氧化物酶可基于与其发生反应的特定的卤化物或硫氰酸盐而不同。例如,髓过氧化物酶使用Cl”,Br”,I”或SCN”作为电子供体,并使其发生氧化而形成抗菌的次卤化物或次硫氰酸盐。乳过氧化物酶催化Br”,I”或SCN”的氧化以产生抗菌产物,但不会催化Cl”的氧化。辣根过氧化物酶仅使用I”作为电子供体以产生I2,HIO和IO”。Peroxidases present in hydrogen peroxide and peroxidases present in halides or thiocyanates can act as electron donors to produce products with a variety of different antibacterial properties. Peroxidases can vary based on the specific halides or thiocyanates they react with. For example, myeloperoxidase uses Cl⁻, Br⁻, I⁻, or SCN⁻ as electron donors and oxidizes them to form antibacterial hypohalides or hypothiocyanates. Lactoperoxidase catalyzes the oxidation of Br⁻, I⁻, or SCN⁻ to produce antibacterial products, but does not catalyze the oxidation of Cl⁻. Horseradish peroxidase uses only I⁻ as an electron donor to produce I₂, HIO, and IO.

优选使用的过氧化物酶是乳过氧化物酶。The preferred peroxidase to use is lactoperoxidase.

所述酶可以是固定的或非固定的。术语“固定的”是指酶附着至惰性的不可溶的材料(例如,海藻酸钙)。这可使得对诸如pH或温度之类的条件的改变的耐受性提高。术语“非固定的”是指酶是游离的。The enzyme can be fixed or non-fixed. The term "fixed" means that the enzyme is attached to an inert, insoluble material (e.g., calcium alginate). This allows for increased tolerance to changes in conditions such as pH or temperature. The term "non-fixed" means that the enzyme is free.

固体组合物包含可氧化的底物。其可基于所使用的过氧化物酶来选择。本领域技术人员能够知晓过氧化物酶体系并且理解如果选择了乳过氧化物酶那么可氧化的底物将会是硫氰酸根离子或碘离子(或者它们的混合物)。在另一实例中,如果使用了髓过氧化物酶,那么需要硫氰酸根离子,碘离子或氯离子(或者它们的混合物)。The solid composition contains an oxidizable substrate. This substrate can be selected based on the peroxidase used. Those skilled in the art will recognize peroxidase systems and understand that if lactoperoxidase is selected, the oxidizable substrate will be thiocyanate ions or iodide ions (or a mixture thereof). In another example, if myeloperoxidase is used, then thiocyanate ions, iodide ions, or chloride ions (or a mixture thereof) are required.

可氧化物的底物选自:带负电荷的卤素及其衍生物,或拟卤素及其衍生物。术语“带负电荷的卤素”是指氯化物和碘化物。虽然可以使用溴化物,但是溴化物不是优选的。拟卤素是卤素的多原子类似物,其化学性质类似于真正的卤素并且在若干类型的化学化合物中其可替代卤素。拟卤素出现在拟卤素分子中。拟卤素的实例包括:次硫氰酸盐,异硫氰酸盐和硫氰酸盐。术语“衍生物”是指其盐。The substrates for oxidizable compounds are selected from negatively charged halogens and their derivatives, or pseudohalogens and their derivatives. The term "negatively charged halogen" refers to chlorides and iodides. Although bromides can be used, they are not preferred. Pseudohalogens are polyatomic analogs of halogens that have chemical properties similar to true halogens and can substitute for halogens in several types of chemical compounds. Pseudohalogens appear in pseudohalogen molecules. Examples of pseudohalogens include hypothiocyanates, isothiocyanates, and thiocyanates. The term "derivative" refers to its salt.

可氧化的底物选自:Oxidizable substrates are selected from:

(i)卤素,例如,氯化物,例如,氯化钠;碘化物,例如,碘化钾和碘化钠,或(i) Halogens, for example, chlorides, such as sodium chloride; iodides, such as potassium iodide and sodium iodide, or

(ii)拟卤素盐,其选自:硫氰酸钠,硫氰酸钾,亚硫酸氢钠,次硫酸钠,偏亚硫酸氢钠,亚硝酸钠,亚硝酸钾,次氯酸钠。(ii) pseudohalogen salts selected from: sodium thiocyanate, potassium thiocyanate, sodium bisulfite, sodium hyposulfite, sodium metabisulfite, sodium nitrite, potassium nitrite, sodium hypochlorite.

优选地,可氧化的底物选自:硫氰酸钠,硫氰酸钾和碘化钾及其组合。Preferably, the oxidizable substrate is selected from sodium thiocyanate, potassium thiocyanate, and potassium iodide, and combinations thereof.

任选地,可氧化的底物可以是被包封的。任选地,氧化剂可以是被包封的。可使用的典型的包封剂包括但不限于:海藻酸盐,壳聚糖,角叉菜胶,树胶(例如,黄原胶)和明胶。包封技术是本领域公知的并且是本领域技术人员可获得的。Optionally, the oxidizable substrate may be encapsulated. Optionally, the oxidant may be encapsulated. Typical encapsulating agents that can be used include, but are not limited to, alginate, chitosan, carrageenan, gums (e.g., xanthan gum), and gelatin. Encapsulation techniques are well known in the art and are available to those skilled in the art.

根据本发明,氧化剂是能够产生过氧化氢的任何化学化合物。对于本发明而言,优选的是,氧化剂是固体形式。氧化剂可选自金属过氧化物,例如,过氧化钙,过氧化镁或过氧化钠。氧化剂还可选自高锰酸盐和过碳酸盐,例如过碳酸钠。According to the present invention, the oxidant is any chemical compound capable of producing hydrogen peroxide. For the purposes of this invention, it is preferred that the oxidant be in solid form. The oxidant may be selected from metal peroxides, such as calcium peroxide, magnesium peroxide, or sodium peroxide. The oxidant may also be selected from permanganates and percarbonates, such as sodium percarbonate.

氧化剂也可以是葡聚糖和葡萄糖氧化酶的组合。这些氧化酶产生过氧化氢和副产物葡萄糖酸内脂。葡萄糖酸内脂产生的酸性在降低其pH值方面是有利的。在低pH条件下产生的活性剂被认为是次硫氰酸并且其也被认为具有比衍生物更强的抗菌作用。在最优pH5.3的条件下,次硫氰酸盐离子与次硫氰酸达到平衡。不带电荷的次硫氰酸被认为是两种形式中具有更好的杀菌作用(Thomas EL,Pera KA,Smith KW,Chwang AK(1983年2月)."Inhibition of Streptococcus mutans by the lactoperoxidase antimicrobialsystem".Infect.Immun.39(2):767–78.PMC 348016.PMID 6832819)。Oxidizing agents can also be a combination of dextran and glucose oxidase. These oxidases produce hydrogen peroxide and the byproduct gluconolactone. The acidity produced by gluconolactone is advantageous in lowering its pH. The active agent produced under low pH conditions is considered to be hypothiocyanate and it is also considered to have stronger antibacterial activity than its derivatives. Under optimal pH 5.3, hypothiocyanate ions reach equilibrium with hypothiocyanate. Uncharged hypothiocyanate is considered to have better bactericidal activity of the two forms (Thomas EL, Pera KA, Smith KW, Chwang AK (February 1983). "Inhibition of Streptococcus mutans by the lactote oxidase antimicrobial system". Infect. Immun. 39(2):767–78. PMC 348016. PMID 6832819).

优选地,氧化剂选自:过氧化钙和过碳酸钠。本申请的申请人已经发现过氧化钙和过碳酸钠溶解于水中会释放出25%至30%的活性氧(类似于直接使用过氧化氢的有效性)。值得注意的是,过氧化钙和过碳酸钠均可用作食品可用的成分。Preferably, the oxidant is selected from calcium peroxide and sodium percarbonate. The applicant of this application has discovered that calcium peroxide and sodium percarbonate, when dissolved in water, release 25% to 30% of reactive oxygen species (similar to the effectiveness of directly using hydrogen peroxide). It is noteworthy that both calcium peroxide and sodium percarbonate can be used as food-grade ingredients.

根据本发明,固体组合物还可包括至少一种惰性填充物,其选自微晶纤维素,碳酸钙,一水合葡聚糖,硬脂酸镁,磷酸二钙,乳糖粉末,多功能淀粉,部分解聚纤维素,部分预糊化淀粉,高功能淀粉,膨润土以及它们的组合。According to the present invention, the solid composition may further include at least one inert filler selected from microcrystalline cellulose, calcium carbonate, dextran monohydrate, magnesium stearate, dicalcium phosphate, lactose powder, multifunctional starch, partially depolymerized cellulose, partially pregelatinized starch, high-performance starch, bentonite, and combinations thereof.

对于惰性填充物(或赋形剂)而言,其是指非活性化学底物,其用于增大包含一种或多种强效活性成分的固体制剂的体积。申请人已经发现在包含诸如硫氰酸盐之类的可氧化的底物的组合物中水分含量增加,其可能会导致凝结。这可能会使得组合物难以溶解于水。为了克服这个问题,可以使用惰性填充物。而且,由于少量填充胶囊和小袋的填充精确度总是不高,所以使用惰性填充物。Inert fillers (or excipients) refer to inactive chemical substrates used to increase the volume of solid dosage forms containing one or more potent active ingredients. The applicant has found that increased moisture content in compositions containing oxidizable substrates such as thiocyanates can lead to coagulation. This can make the composition difficult to dissolve in water. Inert fillers can be used to overcome this problem. Furthermore, inert fillers are used because the filling accuracy of small-volume capsules and sachets is always not high.

优选地,所述惰性填充物是微晶纤维素(MCC)。这种类型的惰性填充物是非常有用的,因为其既是食品级别的也是药品级别的。此外,其可吸收水分。还可使用其他类似类型的惰性填充物。Preferably, the inert filler is microcrystalline cellulose (MCC). This type of inert filler is very useful because it is both food-grade and pharmaceutical-grade. Furthermore, it absorbs moisture. Other similar types of inert fillers can also be used.

任选地,惰性填充物是二氧化硅。这种类型的惰性填充物对于吸收水分而言也是有用的,因此能够保持固体组合物的组分更加干燥并且维持化合物的稳定性。Optionally, the inert filler is silica. This type of inert filler is also useful for absorbing moisture, thus keeping the components of the solid composition drier and maintaining the stability of the compound.

在本发明的另一方面,不存在惰性填充物。In another aspect of the invention, there is no inert filler.

根据本发明,固体组合物还包括缓冲体系。缓冲剂是一种能够耐受pH的急剧变化的溶液。缓冲剂的这种耐受能力是因为其是由某些溶质对组成的,例如,弱酸和衍生自弱酸的盐或弱碱和弱碱的盐。缓冲剂是本领域公知的。术语“缓冲体系”是指一种固体缓冲组合物,其包含例如,酸和盐,例如,柠檬酸盐和柠檬酸三钠。当将该缓冲体系加至水中时,缓冲体系形成缓冲溶液。According to the present invention, the solid composition further includes a buffer system. A buffer is a solution capable of withstanding rapid changes in pH. This tolerance of the buffer is due to its composition of certain solute pairs, for example, a weak acid and a salt derived from the weak acid, or a weak base and a salt of the weak base. Buffers are well known in the art. The term "buffer system" refers to a solid buffer composition comprising, for example, an acid and a salt, such as a citrate and trisodium citrate. When this buffer system is added to water, the buffer system forms a buffer solution.

可存在于缓冲体系中的盐的类型包括但不限于:柠檬酸盐,硼酸盐,碳酸盐和磷酸盐。也可使用其他有机酸的盐,包括但不限于:醋酸,马来酸,乳酸和酒石酸。The types of salts that can be present in the buffer system include, but are not limited to, citrates, borates, carbonates, and phosphates. Salts of other organic acids may also be used, including but not limited to, acetic acid, maleic acid, lactic acid, and tartaric acid.

优选地,缓冲体系使得固体组合物制备成溶液后的pH在起始阶段降至低于或等于6.5,随后使pH升高至高于或等于7.5。低pH对于开始产生次硫氰酸盐离子而言是最优的,同时,较高的pH随后稳定产生的次硫氰酸盐离子。添加/使用缓冲剂来稳定并控制pH能够产生较高的起始次硫氰酸盐值,而且还能够稳定溶液中的次硫氰酸盐持续若干小时。Preferably, the buffer system causes the pH of the solid composition, after being prepared into a solution, to initially drop to below or equal to 6.5, and then raise the pH to above or equal to 7.5. A low pH is optimal for the initial formation of hypothiocyanate ions, while a higher pH subsequently stabilizes the formed hypothiocyanate ions. Adding/using a buffer to stabilize and control the pH results in a higher initial hypothiocyanate value and also stabilizes the hypothiocyanate in the solution for several hours.

任选地,缓冲体系选自如下体系:Optionally, the buffer system may be selected from the following systems:

柠檬酸:柠檬酸三钠Citric acid: trisodium citrate

乳酸钙:柠檬酸Calcium lactate: Citric acid

无水L(+)-酒石酸钠:柠檬酸Anhydrous L(+)-sodium tartrate:citric acid

乳酸钙:DL-马来酸Calcium lactate: DL-maleic acid

L(+)-酒石酸钠:酒石酸。L(+)-Sodium tartrate: Tartaric acid.

然而,缓冲体系并不被限制于如上列出的体系,其他缓冲体系也可以使用。However, the buffering system is not limited to the systems listed above; other buffering systems can also be used.

在一些实例中,缓冲体系的量为0.5g至0.9g。缓冲体系的量取决于所选择的具体组分而发生改变并且与期望的产物的最终使用相匹配。In some instances, the amount of buffer system is between 0.5 g and 0.9 g. The amount of buffer system varies depending on the specific components selected and is matched to the desired final use of the product.

在一些实例中,如果存在缓冲体系的话,组合物还包含易吸湿的惰性填充物,由此降低缓冲体系对所存在的任何水分的敏感性。在一些实例中,所述惰性填充物是二氧化硅。In some instances, if a buffering system is present, the composition also includes a hygroscopic, inert filler, thereby reducing the sensitivity of the buffering system to any moisture present. In some instances, the inert filler is silica.

在一些实例中,固体组合物不包含缓冲体系,并且缓冲体系或缓冲剂可单独地添加至包含本文所述的固体组合物的水性体系中。In some instances, the solid composition does not contain a buffering system, and the buffering system or buffering agent may be added separately to an aqueous system containing the solid composition described herein.

优选地,所述固体组合物不包含:Preferably, the solid composition does not contain:

(i)促凝剂;(i) accelerators;

(ii)增稠剂,优选地,其中,固体组合物不包含诸如膨润土之类的黏土;和/或(ii) a thickener, preferably wherein the solid composition does not contain clay such as bentonite; and/or

(iii)絮凝剂。(iii) Flocculants.

本领域已知这些类型的组分可用于过氧化酶体系中,以支持反应介质,但是这些组分随后在反应结束时被分离并除去。通常使用诸如聚合氯化铝之类的促凝剂。然而,当含有这种含金属的促凝剂的溶液可能会接触食品或饮品时,这种含金属的促凝剂是不理想的。而且,如果/当将水排入污水体系中时需要避免金属对水的污染。These types of components are known in the art to be used in peroxidase systems to support the reaction medium, but these components are subsequently separated and removed at the end of the reaction. Coagulants such as polyaluminum chloride are typically used. However, such metal-containing coagulants are undesirable when solutions containing them may come into contact with food or beverages. Furthermore, it is necessary to avoid metal contamination of water if/when discharging water into a wastewater system.

在本发明中避免使用的典型促凝剂包括铝盐或铁盐,其包括但不限于氯化铝,氯化铁和多羟基氯化铝。Typical coagulants that are avoided in this invention include aluminum or iron salts, including but not limited to aluminum chloride, ferric chloride, and polyhydroxyaluminum chloride.

在本发明中避免使用的典型絮凝剂包括阴离子或阳离子聚合絮凝剂,例如,多糖或聚丙烯酰胺。申请人已经发现絮凝剂(以及增稠剂)的使用可导致活性物质(例如,次硫氰酸盐)的减少。Typical flocculants avoided in this invention include anionic or cationic polymeric flocculants, such as polysaccharides or polyacrylamide. The applicant has found that the use of flocculants (and thickeners) can lead to a reduction in active substances (e.g., hypothiocyanates).

虽然可能能够使用膨润土作为惰性填充物,但是本发明中避免使用典型的增稠剂。优选地,诸如黏土,高岭土,二氧化硅或硅酸盐之类的增稠剂不存在于本发明中。申请人已经发现诸如膨润土之类的增稠剂通常可能会导致颜色沉积,这在加入水中,尤其是加入饮用水中时,是不理想的。While bentonite could potentially be used as an inert filler, typical thickeners are avoided in this invention. Preferably, thickeners such as clay, kaolin, silica, or silicates are not present in this invention. The applicant has found that thickeners such as bentonite often cause color deposition, which is undesirable when added to water, especially drinking water.

在优选的方面,本发明包括:In a preferred aspect, the present invention includes:

(a)乳过氧化物酶,(a) lactoperoxidase,

(b)硫氰酸钠和/或硫氰酸钾和/或碘化钾,(b) Sodium thiocyanate and/or potassium thiocyanate and/or potassium iodide

(c)过氧化钙,(c) Calcium peroxide,

(d)微晶纤维素,和(d) Microcrystalline cellulose, and

(e)缓冲体系。(e) Buffer system.

所述缓冲体系是根据本文所述的缓冲体系。优选地,所述缓冲体系是柠檬酸:柠檬酸三钠缓冲体系。The buffer system is the buffer system described herein. Preferably, the buffer system is a citric acid:trisodium citrate buffer system.

在根据本发明的进一步的方面,本发明提供一种试剂盒,其包含:In a further aspect of the present invention, a kit is provided comprising:

第一固体组合物,其包含:A first solid composition comprising:

(a)过氧化物酶酶催化剂;(a) Peroxidase enzyme catalyst;

(b)可氧化的底物,其选自:(b) Oxidizable substrates selected from:

(i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or

(ii)拟卤素及其衍生物;以及(ii) pseudohalogens and their derivatives; and

(c)任选地,至少一种惰性填充物,(c) Optionally, at least one inert filler,

(d)任选地,缓冲体系;以及(d) Optionally, a buffer system; and

第二固体组合物,其包含:The second solid composition comprises:

(a)至少一种氧化剂;和(a) at least one oxidizing agent; and

(b)任选地,至少一种惰性填充物。(b) Optionally, at least one inert filler.

根据本发明的试剂盒包含:The kit according to the present invention comprises:

第一固体组合物,其包含:A first solid composition comprising:

(a)过氧化物酶酶催化剂,其含量为所述第一固体组合物的重量的5wt%至45wt%;(a) Peroxidase enzyme catalyst, the content of which is 5 wt% to 45 wt% of the weight of the first solid composition;

(b)可氧化的底物,其含量为所述第一固体组合物的重量的5wt%至55wt%并且其选自:(b) an oxidizable substrate, comprising 5 wt% to 55 wt% of the weight of the first solid composition and selected from:

(i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or

(ii)拟卤素及其衍生物;以及(ii) pseudohalogens and their derivatives; and

(c)任选地,至少一种惰性填充物,其含量为第一固体组合物的0wt%至90wt%,和(c) Optionally, at least one inert filler, in an amount of 0 wt% to 90 wt% of the first solid composition, and

第二固体组合物,其包含:The second solid composition comprises:

(a)至少一种氧化剂,其含量为所述第二固体组合物的重量的5wt%至100wt%,和(a) at least one oxidizing agent, wherein the content is from 5 wt% to 100 wt% of the weight of the second solid composition, and

(b)任选地,至少一种惰性填充物,其含量为所述第二固体组合物的重量的0wt%至95wt%。(b) Optionally, at least one inert filler, in an amount of 0 wt% to 95 wt% of the weight of the second solid composition.

如果所述第一固体组合物包含缓冲体系,其含量高达所述第一固体组合物的40wt%并且所述惰性填充物的含量相应地降低至高达所述第一固体组合物的40wt%。If the first solid composition contains a buffer system, the content of which is up to 40 wt% of the first solid composition, and the content of the inert filler is correspondingly reduced to up to 40 wt% of the first solid composition.

根据本发明,本文提供一种试剂盒,其包含:According to the present invention, a kit is provided comprising:

第一固体组合物,其包含:A first solid composition comprising:

(a)过氧化物酶酶催化剂;(a) Peroxidase enzyme catalyst;

(b)任选地,至少一种惰性填充物,(b) Optionally, at least one inert filler,

第二固体组合物,其包含:The second solid composition comprises:

(c)可氧化的底物,其选自:(c) Oxidizable substrates selected from:

(i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or

(ii)拟卤素及其衍生物,以及(ii) pseudohalogens and their derivatives, and

(d)任选地,至少一种惰性填充物,和(d) Optionally, at least one inert filler, and

第三固体组合物,其包含:The third solid composition comprises:

(e)至少一种氧化剂,和(e) at least one oxidizing agent, and

(f)任选地,至少一种惰性填充物。(f) Optionally, at least one inert filler.

根据本发明,本文提供一种试剂盒,其包含:According to the present invention, a kit is provided comprising:

第一固体组合物,其包含:A first solid composition comprising:

(a)过氧化物酶酶催化剂,其含量为所述第一固体组合物的重量的3wt%至100wt%,(a) a peroxidase catalyst, comprising 3 wt% to 100 wt% of the weight of the first solid composition.

(b)任选地,至少一种惰性填充物,其含量为所述第一固体组合物的重量的0wt%至97wt%,(b) Optionally, at least one inert filler, in an amount of 0 wt% to 97 wt% of the weight of the first solid composition.

第二固体组合物,其包含:The second solid composition comprises:

(c)可氧化的底物,其含量为所述第二固体组合物的重量的3wt%至100wt%,其选自:(c) An oxidizable substrate, comprising 3 wt% to 100 wt% of the weight of the second solid composition, selected from:

(i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or

(ii)拟卤素及其衍生物,以及(ii) pseudohalogens and their derivatives, and

(d)任选地,至少一种惰性填充物,其含量为所述第二固体组合物的重量的0wt%至97wt%,和(d) Optionally, at least one inert filler, in an amount of 0 wt% to 97 wt% of the weight of the second solid composition, and

第三固体组合物,其包含:The third solid composition comprises:

(e)至少一种氧化剂,其含量为所述第三固体组合物的重量的3wt%至100wt%;(e) at least one oxidizing agent, in an amount of 3 wt% to 100 wt% of the weight of the third solid composition;

(f)任选地,至少一种惰性填充物,其含量为所述第三固体组合物的重量的0wt%至97wt%。(f) Optionally, at least one inert filler, in an amount of 0 wt% to 97 wt% of the weight of the third solid composition.

如果所述第二固体组合物包含缓冲体系,那么该缓冲体系的含量高达所述第二固体组合物的重量的40wt%,并且相应地,所述惰性填充物的含量降低至高达所述第二固体组合物的重量的57wt%。If the second solid composition contains a buffer system, then the content of the buffer system is up to 40 wt% of the weight of the second solid composition, and correspondingly, the content of the inert filler is reduced to up to 57 wt% of the weight of the second solid composition.

上文列出的各个组分的重量百分含量无意对本发明进行限定并且其被包括在本发明的范围内以提供实例。每个组合物中每个组分的含量可基于所选择的特定组分而发生改变并且匹配期望的产品的最终使用。The weight percentages of the components listed above are not intended to limit the invention and are included within the scope of the invention to provide examples. The content of each component in each composition may be varied based on the specific components selected and to match the desired end use of the product.

所述试剂盒提供一种多容器产品,这使得多个活性成分可存放至最大保存期。优选地,第一,第二和第三(如果存在的话)组合物中的每一个被装在小袋中,容器中或胶囊中。优选地,如果容器是瓶子的话,其由塑料或玻璃制成。胶囊可由生物可降解材料制成。当固体组合物为单一制剂时,其也可装在小袋中,容器中或胶囊中。The kit provides a multi-container product, which allows multiple active ingredients to be stored to their maximum shelf life. Preferably, each of the first, second, and third (if present) compositions is packaged in a sachet, container, or capsule. Preferably, if the container is a bottle, it is made of plastic or glass. The capsules may be made of biodegradable materials. When the solid composition is a single formulation, it may also be packaged in a sachet, container, or capsule.

固体组合物可存在于单个容器中。具体而言,如果所使用的多个成分中的一个或多个是固定的或包封的,这些成分可形成相同的固体组合物的一部分。单独的小袋,容器或胶囊的使用使得活性成分被分开保存,因此提高了固体组合物的保存期。这也确保了各个试剂之间不会发生不想要的反应。Solid compositions can exist in a single container. Specifically, if one or more of the multiple ingredients used are fixed or encapsulated, these ingredients can form part of the same solid composition. The use of individual sachets, containers, or capsules allows the active ingredients to be stored separately, thus increasing the shelf life of the solid composition. This also ensures that unwanted reactions do not occur between the individual agents.

小袋、容器或胶囊可保存第一、第二和第三固体组合物。当试剂盒包含单独的小袋时,优选地,第一、第二和第三固体组合物中的每一个的量为0.2g至2.0g(因为这对于药物产品而言是理想的)。优选地,其中,试剂盒中单个,两个或三个小袋/胶囊/容器中的每个的总重量为0.6g至6.0g。然而,每个小袋,容器或胶囊中组合物的量不限于该重量并且可根据情况发生改变。任选地,如果准备了一个2g的小袋,并且存在缓冲体系的话,那么缓冲体系的量为0.5g至0.9g。The sachets, containers, or capsules may contain the first, second, and third solid compositions. When the kit contains individual sachets, preferably, the amount of each of the first, second, and third solid compositions is 0.2 g to 2.0 g (as this is ideal for pharmaceutical products). Preferably, the total weight of each of the single, two, or three sachets/capsules/containers in the kit is 0.6 g to 6.0 g. However, the amount of composition in each sachet, container, or capsule is not limited to this weight and may vary depending on the circumstances. Optionally, if a 2 g sachet is prepared and a buffer system is present, then the amount of the buffer system is 0.5 g to 0.9 g.

优选地,第一、第二和第三固体组合物的保存期超过两年(这对于药物和化妆品而言是理想的并且在大多数其他工业领域中也是理想的)。Preferably, the first, second and third solid compositions have a shelf life of more than two years (which is ideal for pharmaceuticals and cosmetics and in most other industrial sectors).

为了制备水性体系(下文也称为水性溶液),用户可将单一制剂形式的固体组合物简单地添加至水中或将多种组合物(如上所述)加至水中。如果需要的话,搅拌含有固体组合物的水性溶液或晃动含有固体组合物的水性溶液以使得各个成分溶解并激活反应。To prepare an aqueous system (hereinafter also referred to as an aqueous solution), the user can simply add a single formulation of the solid composition to water or add multiple compositions (as described above) to water. If necessary, the aqueous solution containing the solid composition is stirred or shaken to dissolve the components and activate the reaction.

水可以是自来水,蒸馏水,去离子水,逆向渗透水或瓶装水。水可以是装在诸如储罐之类的大型容器中的水。待处理的水的体积不受任何限制。如本文所述的,甚至可通过控制向流动的水中添加固体组合物来产生连续液流。The water can be tap water, distilled water, deionized water, reverse osmosis water, or bottled water. The water can be stored in large containers such as storage tanks. There are no restrictions on the volume of water to be treated. As described herein, even continuous flow can be generated by controlling the addition of solid compositions to flowing water.

装在小袋,容器或胶囊中的成分的量取决于水性体系的需求和水的体积。然而,为了易于操作和精确加料(例如,加至小袋和胶囊中),通常使用较小量的产品。The amount of ingredient contained in a sachet, container, or capsule depends on the requirements of the aqueous system and the volume of water. However, smaller quantities of product are typically used for ease of handling and precise dosing (e.g., into sachets and capsules).

如上所述,第一,第二和第三固体组合物可装在单独的小袋或容器中。当制备水性溶液时,将第一固体组合物加至水中,随后加入第二固体组合物,然后任选地加入第三组合物(如果存在的话)。然后可混合水性溶液。所述溶液可被混合持续高达30分钟,例如25分钟,20分钟或15分钟。混合之后,溶液可静置1分钟至20分钟,随后使用。发明人已经发现通过使水性溶液在混合之后静置,次硫氰酸盐离子的稳定性和溶液的保存期得以提高。As described above, the first, second, and third solid compositions can be packaged in separate pouches or containers. When preparing an aqueous solution, the first solid composition is added to water, followed by the second solid composition, and then optionally the third composition (if present). The aqueous solution can then be mixed. The solution can be mixed for up to 30 minutes, for example, 25 minutes, 20 minutes, or 15 minutes. After mixing, the solution can be allowed to stand for 1 to 20 minutes before use. The inventors have discovered that allowing the aqueous solution to stand after mixing improves the stability of hypothiocyanate ions and the shelf life of the solution.

根据本发明,水性体系用作抗菌溶液,杀菌溶液,抗真菌溶液和抗病毒溶液。水性体系还可用于:According to the present invention, the aqueous system is used as an antibacterial solution, a bactericidal solution, an antifungal solution, and an antiviral solution. The aqueous system can also be used for:

(i)对包括表面在内的材料进行清洁,洗涤和杀菌;(i) Cleaning, washing and sterilizing materials, including surfaces;

(ii)制备需要用于药品和化妆品的溶液;(ii) Prepare solutions that are intended for use in pharmaceuticals and cosmetics;

(iii)引入空气中并施用于表面以杀灭致病菌;(iii) Introduce into the air and apply to surfaces to kill pathogens;

(iv)产生细喷雾或气雾随后被人和/动物吸入。(iv) It produces a fine spray or mist that is then inhaled by humans and/or animals.

本发明的另一个目的还在于单独使用本文所述的固体组合物或水性体系的一部分或将本文所述的固体组合物或水性体系的一部分与其他抗感染剂,抗菌剂,抗病毒剂,抗生素,抗真菌剂或防腐剂联合使用,用于材料、表面、仪器和医疗设备的杀菌和消毒。例如,水性体系可用在手术室以对其中的表面或仪器进行杀菌。Another object of the present invention is to use alone or in combination with other anti-infective agents, antibacterial agents, antiviral agents, antibiotics, antifungal agents, or preservatives a portion of the solid compositions or aqueous systems described herein for the sterilization and disinfection of materials, surfaces, instruments, and medical devices. For example, the aqueous system can be used in operating rooms to sterilize surfaces or instruments therein.

可选地,本发明的水性溶液可用于空气处理,例如飞机舱内的空气净化(被动),大气净化(主动)和环境清洁。Optionally, the aqueous solution of the present invention can be used for air treatment, such as air purification (passive) in aircraft cabins, atmospheric purification (active) and environmental cleaning.

本发明还涉及单独使用本文所述的本发明的固体组合物或水性体系的一部分或者将本文所述的本发明的固体组合物或水性体系的一部分与其他抗感染剂,抗菌剂,抗病毒剂,抗生素,抗真菌剂或防腐剂联合使用,用于处理食品或饮用水,景观用水和用于随后的抗菌应用的水。The present invention also relates to the use of a portion of the solid compositions or aqueous systems of the present invention, either alone or in combination with other anti-infective agents, antimicrobial agents, antiviral agents, antibiotics, antifungal agents, or preservatives, for the treatment of food or drinking water, landscaping water, and water for subsequent antimicrobial applications.

本发明还涉及单独使用所述固体组合物或使所述固体组合物和其他抗感染剂,抗菌剂,抗病毒剂联合使用,用于除去农业中的致病菌,其以喷雾或水雾的形式用于花田或农作物或用于温室或用于易变质物品的存储设施中。The present invention also relates to the use of the solid composition alone or in combination with other anti-infective agents, antibacterial agents, and antiviral agents for the removal of pathogens in agriculture, in the form of sprays or mists, in flower fields or crops, or in greenhouses or in storage facilities for perishable goods.

本发明还涉及单独使用所述组合物或将所述组合物与其他抗感染剂,抗菌剂,抗病毒剂,抗生素,抗真菌剂或防腐剂联合使用,用于与清洁剂或杀菌剂共同使用。The present invention also relates to the use of the composition alone or in combination with other anti-infective agents, antibacterial agents, antiviral agents, antibiotics, antifungal agents or preservatives, for use with cleaning agents or disinfectants.

制备得到的水性溶液的改善的稳定性和保存期还使得产品被用于需要使用大量溶液的情况或需要含有活性物质的水性溶液具有长期稳定性的情况。例如,可大量制备水性溶液并且将其用于田地中的水厂(这通常需要花费农夫几个小时的时间),从而使用连续的水性溶液液流来洗涤蔬菜或在食品仓库的空气中喷洒水雾。The improved stability and shelf life of the prepared aqueous solution also make the product suitable for applications requiring large quantities of solution or where long-term stability of the aqueous solution containing active ingredients is needed. For example, the aqueous solution can be prepared in large quantities and used in water treatment plants in fields (which typically takes farmers several hours), allowing for the use of a continuous stream of aqueous solution to wash vegetables or spray water mist in the air of food warehouses.

本发明提供一种对水进行消毒的方法,其包括如下步骤:This invention provides a method for disinfecting water, comprising the following steps:

(i)将本文所述的固体组合物添加至待消毒的水中,或(i) Add the solid composition described herein to the water to be disinfected, or

(ii)使用本文所述的试剂盒,其中,将第一和第二固体组合物添加至待消毒的水中,或(ii) Using the kit described herein, wherein the first and second solid compositions are added to the water to be disinfected, or

(iii)将本文所述的水性体系添加至待消毒的水中。(iii) Add the aqueous system described herein to the water to be disinfected.

本发明提供一种制备抗菌溶液,杀菌溶液,杀真菌溶液和抗病毒溶液的方法,其包括如下步骤:This invention provides a method for preparing antibacterial solutions, bactericidal solutions, antifungal solutions, and antiviral solutions, comprising the following steps:

(i)将本文所述的固体组合物添加至水中,或(i) Adding the solid composition described herein to water, or

(ii)使用本文所述的试剂盒,其中,将第一,第二和任选的第三固体组合物添加至水中,(ii) Using the kit described herein, wherein the first, second, and optionally third solid compositions are added to water,

(iii)任选地,还添加其他抗感染剂,抗菌剂,抗病毒剂,抗生素,抗真菌剂,防腐剂和杀菌剂。(iii) Optionally, other anti-infective agents, antibacterial agents, antiviral agents, antibiotics, antifungal agents, preservatives and bactericides may also be added.

根据本发明制备的溶液的活性物质的目标浓度为50ppm至95ppm。这是已知的最稳定的初始产品水平并且就抗致病菌活性而言这也是较强的反应水平,尤其是在溶液中。25ppm以下几乎没有抗致病菌活性,而且杀死的致病菌可很快地被已存在的致病菌的生长所替代。The target concentration of the active substance in the solution prepared according to the present invention is 50 ppm to 95 ppm. This is the most stable initial product level known and also a relatively strong reaction level in terms of antipathogenic activity, especially in solution. Below 25 ppm, there is almost no antipathogenic activity, and the killed pathogens can be quickly replaced by the growth of existing pathogens.

在空气中,目标活性将会是25ppm至50ppm,其看起来有效降低致病菌并且对于人和动物的吸入或皮肤接触而言处于安全水平。In the air, the target activity would be 25 ppm to 50 ppm, which appears to effectively reduce pathogens and is at a safe level for inhalation or skin contact with humans and animals.

本发明的发明人还发现活性物质的水平可提高至120ppm,包括缓冲剂在内(如下文实施例和附图所显示的)。The inventors of this invention have also discovered that the level of the active substance can be increased to 120 ppm, including the buffer (as shown in the examples and figures below).

实施例Example

试剂盒的制备Preparation of reagent kit

在本实施例中制备了如下试剂盒:The following reagent kit was prepared in this embodiment:

第一容器(总重量0.5g):0.2g LPO,0.118g NaSCN,0.182g微晶纤维素First container (total weight 0.5g): 0.2g LPO, 0.118g NaSCN, 0.182g microcrystalline cellulose

第二容器(总重量0.5g):0.104g CaO2,0.396g微晶纤维素Second container (total weight 0.5g): 0.104g CaO 2 , 0.396g microcrystalline cellulose

在上述粉末量/500mL水的条件下进行测试。图1显示了该实验的放大实验,其中,测试了在4℃下储存120小时过程中在5L溶液中的次硫氰酸盐离子的量。附图显示,产品维持令人满意的次硫氰酸盐水平超过40个小时。The test was conducted under the conditions of powder volume/500 mL water. Figure 1 shows a scaled-up experiment in which the amount of hypothiocyanate ions in a 5 L solution was tested during storage at 4 °C for 120 hours. The figure shows that the product maintained a satisfactory hypothiocyanate level for more than 40 hours.

图2显示了过氧化钙和过碳酸钠在次硫氰酸盐稳定性方面的作用的比较。图2显示,与使用过氧化钙在整个24小时的储存时间的反应相比,使用过碳酸钠在最初的5个小时提供较低水平的次硫氰酸盐稳定性,其随后上升并维持在较高水平。然而,使用这两者均能够实现令人满意的稳定性水平。Figure 2 shows a comparison of the effects of calcium peroxide and sodium percarbonate on hypothiocyanate stability. Figure 2 indicates that, compared to the reaction using calcium peroxide over a 24-hour storage period, sodium percarbonate provided a lower level of hypothiocyanate stability in the initial 5 hours, which subsequently increased and remained at a higher level. However, satisfactory levels of stability could be achieved using both.

本实施例中还制备了如下试剂盒:The following reagent kit was also prepared in this embodiment:

缓冲剂的优化&稳定性Buffer optimization & stability

对缓冲体系进行了测试以确定是否能够获得较高的次硫氰酸盐水平。对如上制备的试剂盒(请参考附图1和附图2的讨论)进行了测试并且其中包括了6.5mMol柠檬酸:柠檬酸三钠缓冲剂。The buffer system was tested to determine if a high level of hypothiocyanate could be obtained. The kit prepared as described above (see the discussion in Figures 1 and 2) was tested and included a 6.5 mmol citric acid:trisodium citrate buffer.

将上述容器1的成分混合10分钟。加入容器2的组分(包含上文所述的固体组合物,0.104g CaO2,0.396g微晶纤维素,以及缓冲剂),加水达到总体积330ml。容器2混合15分钟。值得注意的是,在6.5mM缓冲的测试中加入容器2之后观察到pH发生了显著下降。Mix the components of container 1 for 10 minutes. Add the components of container 2 (containing the solid composition described above, 0.104 g CaO 2 , 0.396 g microcrystalline cellulose, and buffer), and add water to reach a total volume of 330 ml. Mix container 2 for 15 minutes. Notably, a significant decrease in pH was observed after adding container 2 in the 6.5 mM buffer test.

图3显示了在使用缓冲的过氧化钙时产生提高的次硫氰酸盐水平。Figure 3 shows the increased hypothiocyanate levels produced when using buffered calcium peroxide.

图4表明在添加过氧化钙/过碳酸钠并进行混合后静置包含缓冲体系的水性溶液之后,次硫氰酸盐的ppm值增加并且随后保持稳定。Figure 4 shows that after adding calcium peroxide/sodium percarbonate and mixing, and then allowing the aqueous solution containing the buffer system to stand, the ppm value of hypothiocyanate increased and subsequently remained stable.

图5显示在整个混合过程中(总共25分钟)pH发生变化。请注意,KI B是根据本发明制备的产物/水性溶液的名称。Figure 5 shows the pH changes throughout the mixing process (25 minutes in total). Note that KI B is the name of the product/aqueous solution prepared according to the present invention.

上述结果表明,缓冲剂对本发明非常有用,因为其能够产生反应的最优pH曲线。所获得的有益之处包括次硫氰酸盐在溶液中更长的稳定性(高达24小时)。这种较长时间的稳定性在很多领域都是有用的,例如,在农业领域,喷洒田地/作物以解决细菌或病毒问题或对需要无菌环境的医院手术室或等候区域进行清洁杀菌。The above results demonstrate that buffers are highly useful in this invention because they produce an optimal pH profile for the reaction. The benefits obtained include the longer stability of hypothiocyanate in solution (up to 24 hours). This extended stability is useful in many fields, such as in agriculture, spraying fields/crops to address bacterial or viral problems, or cleaning and sterilizing hospital operating rooms or waiting areas requiring a sterile environment.

Claims (20)

1.固体组合物,其包含:1. A solid composition comprising: (a)固定的或非固定的过氧化物酶酶催化剂;(a) Fixed or non-fixed peroxidase catalyst; (b)可氧化的底物,其选自:(b) Oxidizable substrates selected from: (i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or (ii)拟卤素及其衍生物,(ii) Pseudohalogens and their derivatives. (c)至少一种氧化剂;(c) at least one oxidizing agent; (d)任选地,至少一种惰性填充物,和(d) Optionally, at least one inert filler, and (e)任选地,缓冲体系。(e) Optional, buffer system. 2.如权利要求1所述的固体组合物,其中,所述过氧化物酶酶催化剂选自:乳过氧化物酶,髓过氧化物酶,嗜酸性粒细胞过氧化物酶,脲过氧化物酶和衍生自植物的过氧化物酶,优选地,其中,所述酶催化剂是乳过氧化物酶。2. The solid composition of claim 1, wherein the peroxidase catalyst is selected from: lactoperoxidase, myeloperoxidase, eosinophil peroxidase, urea peroxidase and plant-derived peroxidases, preferably, wherein the enzyme catalyst is lactoperoxidase. 3.如权利要求1或2所述的固体组合物,其中,所述可氧化的底物选自:3. The solid composition of claim 1 or 2, wherein the oxidizable substrate is selected from: (i)氯化物,例如,氯化钠;碘化物,例如,碘化钾和碘化钠;或(i) Chlorides, such as sodium chloride; iodides, such as potassium iodide and sodium iodide; or (ii)硫氰酸钠,硫氰酸钾,亚硫酸氢钠,次硫酸钠,偏亚硫酸氢钠,(ii) Sodium thiocyanate, potassium thiocyanate, sodium bisulfite, sodium hyposulfite, sodium metabisulfite 亚硝酸钠,亚硝酸钾,次氯酸钠。Sodium nitrite, potassium nitrite, sodium hypochlorite. 4.如上述权利要求中任一项所述的固体组合物,其中,所述可氧化的底物选自:硫氰酸钠,硫氰酸钾和碘化钾及其组合,任选地,其中,所述可氧化的底物是包封的。4. The solid composition as claimed in any of the preceding claims, wherein the oxidizable substrate is selected from sodium thiocyanate, potassium thiocyanate, and potassium iodide, and combinations thereof, optionally wherein the oxidizable substrate is encapsulated. 5.如上述权利要求中任一项所述的固体组合物,其中,所述氧化剂选自:过氧化钙,过氧化钠,过碳酸钠以及葡聚糖和葡萄糖氧化酶的组合,任选地,其中,所述氧化剂是包封的。5. The solid composition as claimed in any of the preceding claims, wherein the oxidant is selected from: calcium peroxide, sodium peroxide, sodium percarbonate, and combinations of dextran and glucose oxidase, optionally wherein the oxidant is encapsulated. 6.如上述权利要求中任一项所述的固体组合物,其中,所述固体组合物包含:至少一种惰性填充物,其选自:微晶纤维素,碳酸钙,一水合葡聚糖,硬脂酸镁,磷酸二钙,乳糖粉末,多功能淀粉,部分解聚的纤维素,部分预糊化的淀粉,高功能淀粉,膨润土,二氧化硅以及它们的组合。6. The solid composition as claimed in any of the preceding claims, wherein the solid composition comprises: at least one inert filler selected from: microcrystalline cellulose, calcium carbonate, dextran monohydrate, magnesium stearate, dicalcium phosphate, lactose powder, multifunctional starch, partially depolymerized cellulose, partially pregelatinized starch, high-performance starch, bentonite, silica, and combinations thereof. 7.如上述权利要求中任一项所述的固体组合物,其中,所述固体组合物不包含:7. The solid composition as claimed in any of the preceding claims, wherein the solid composition does not contain: (i)促凝剂;(i) accelerators; (ii)增稠剂,优选地,其中,所述固体组合物不包含诸如膨润土之类的黏土,和/或(ii) a thickener, preferably wherein the solid composition does not contain clay such as bentonite, and/or (iii)絮凝剂。(iii) Flocculants. 8.如上述权利要求中任一项所述的固体组合物,其中,所述缓冲体系选自:柠檬酸:柠檬酸三钠;乳酸钙:柠檬酸;L(+)-无水酒石酸钠:柠檬酸;乳酸钙:DL-马来酸:马来酸以及L(+)-酒石酸钠:酒石酸。8. The solid composition as claimed in any one of the preceding claims, wherein the buffer system is selected from: citric acid: trisodium citrate; calcium lactate: citric acid; L(+)-anhydrous sodium tartrate: citric acid; calcium lactate: DL-maleic acid: maleic acid; and L(+)-sodium tartrate: tartaric acid. 9.如权利要求1所述的固体组合物,其中,所述固体组合物包含:9. The solid composition of claim 1, wherein the solid composition comprises: (a)乳过氧化物酶;(a) lactoperoxidase; (b)硫氰酸钠和/或硫氰酸钾和/或碘化钾;(b) Sodium thiocyanate and/or potassium thiocyanate and/or potassium iodide; (c)过氧化钙;(c) Calcium peroxide; (d)微晶纤维素;和(d) Microcrystalline cellulose; and (e)缓冲体系。(e) Buffer system. 10.一种试剂盒,其包含:10. A reagent kit comprising: 第一固体组合物,其包含:A first solid composition comprising: (a)过氧化物酶酶催化剂;(a) Peroxidase enzyme catalyst; (b)可氧化的底物,其选自:(b) Oxidizable substrates selected from: (i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or (ii)拟卤素及其衍生物,以及(ii) pseudohalogens and their derivatives, and (c)任选地,至少一种惰性填充物;(c) Optionally, at least one inert filler; (d)任选地,缓冲体系,(d) Optional, buffer system 第二固体组合物,其包含:The second solid composition comprises: (e)至少一种氧化剂,和(e) at least one oxidizing agent, and (f)任选地,至少一种惰性填充物。(f) Optionally, at least one inert filler. 11.一种试剂盒,其包含:11. A reagent kit comprising: 第一固体组合物,其包含:A first solid composition comprising: (a)过氧化物酶酶催化剂;(a) Peroxidase enzyme catalyst; (b)任选地,至少一种惰性填充物,(b) Optionally, at least one inert filler, 第二固体组合物,其包含:The second solid composition comprises: (c)可氧化的底物,其选自:(c) Oxidizable substrates selected from: (i)带负电荷的卤素及其衍生物,或(i) Negatively charged halogens and their derivatives, or (ii)拟卤素及其衍生物;(ii) pseudohalogens and their derivatives; (d)任选地,至少一种惰性填充物;(d) Optionally, at least one inert filler; (e)任选地,缓冲体系,和(e) Optionally, the buffer system, and 第三固体组合物,其包含:The third solid composition comprises: (f)至少一种氧化剂,和(f) at least one oxidizing agent, and (g)任选地,至少一种惰性填充物。(g) Optionally, at least one inert filler. 12.如权利要求10或11所述的试剂盒,其中:12. The kit according to claim 10 or 11, wherein: 所述过氧化物酶酶催化剂是权利要求2所述的过氧化物酶酶催化剂;The peroxidase catalyst is the peroxidase catalyst according to claim 2; 所述可氧化的底物是权利要求3或4所述的可氧化的底物;The oxidizable substrate is the oxidizable substrate as described in claim 3 or 4; 所述惰性填充物是权利要求6所述的惰性填充物;The inert filler is the inert filler as described in claim 6; 所述氧化剂是权利要求5所述的氧化剂;The oxidizing agent is the oxidizing agent according to claim 5; 所述缓冲体系是权利要求8所述的缓冲体系。The buffer system is the buffer system described in claim 8. 13.如权利要求10至12中任一项所述的试剂盒,其中,所述试剂盒不包含:13. The kit according to any one of claims 10 to 12, wherein the kit does not contain: (i)促凝剂;(i) Accelerators; (ii)增稠剂,优选地,其中,该制剂部包含诸如膨润土之类的黏土;和/或(ii) a thickener, preferably wherein the formulation comprises clay such as bentonite; and/or (iii)絮凝剂。(iii) Flocculants. 14.如权利要求10至13中任一项所述的试剂盒,其中,第一固体组合物和第二固体组合物以及任选的第三固体组合物中的每一个被单独装在小袋、容器或胶囊中。14. The kit according to any one of claims 10 to 13, wherein each of the first solid composition, the second solid composition, and optionally the third solid composition is individually packaged in a sachet, container, or capsule. 15.一种水性体系,其包含权利要求1至9中任一项所述的固体组合物和水。15. An aqueous system comprising the solid composition of any one of claims 1 to 9 and water. 16.如权利要求15所述的水性体系,其中,所述水是自来水,去离子水,蒸馏水,反向渗透水或瓶装水,大体积水或连续流动水。16. The aqueous system of claim 15, wherein the water is tap water, deionized water, distilled water, reverse osmosis water, bottled water, bulk water, or continuously flowing water. 17.如权利要求15或16所述的水性体系,其用作抗菌溶液,杀菌溶液,抗真菌溶液或抗病毒溶液。17. The aqueous system as described in claim 15 or 16, which is used as an antibacterial solution, bactericidal solution, antifungal solution or antiviral solution. 18.如权利要求15至17中任一项所述的水性体系,其用于:18. The aqueous system according to any one of claims 15 to 17, wherein it is used for: (i)对包括表面在内的材料进行清洁、洗涤和杀菌;(i) Cleaning, washing and sterilizing materials, including surfaces; (ii)制备用于药物和化妆品的溶液;(ii) Preparation of solutions for use in pharmaceuticals and cosmetics; (iii)引入空气中并施用于表面以杀死致病菌;以及(iii) Introduced into the air and applied to surfaces to kill pathogens; and (iv)产生细喷雾或水雾,随后由人和/或动物吸入。(iv) Produces a fine spray or mist of water, which is then inhaled by humans and/or animals. 19.一种对水进行消毒的方法,其包括如下步骤:19. A method for disinfecting water, comprising the following steps: (i)将权利要求1至9中任一项所述的固体组合物添加至待消毒的水中,或(i) Adding the solid composition of any one of claims 1 to 9 to the water to be disinfected, or (ii)使用权利要求10至14中任一项所述的试剂盒,其中,将第一固体组合物、第二固体组合物和任选的第三固体组合物加至待消毒的水中,或(ii) Using the kit according to any one of claims 10 to 14, wherein the first solid composition, the second solid composition, and optionally the third solid composition are added to the water to be disinfected, or (iii)将权利要求15或16所述的水性体系加至待消毒的水中。(iii) Add the aqueous system of claim 15 or 16 to the water to be disinfected. 20.一种制备抗菌溶液、杀菌溶液、抗真菌溶液和抗病毒溶液的方法,其包括如下步骤:20. A method for preparing antibacterial solutions, bactericidal solutions, antifungal solutions, and antiviral solutions, comprising the following steps: (i)添加权利要求1至9中任一项所述的固体组合物,或(i) Adding the solid composition according to any one of claims 1 to 9, or (ii)使用权利要求10至14中任一项所述的试剂盒,其中,将第一固体组合物、第二固体组合物和任选的第三固体组合物加至水中,(ii) Using the kit according to any one of claims 10 to 14, wherein the first solid composition, the second solid composition, and optionally the third solid composition are added to water. (iii)任选地,还添加其他抗感染剂,抗菌剂,抗病毒剂,抗生素,抗真菌剂,防腐剂或杀菌剂。(iii) Optionally, other anti-infective agents, antibacterial agents, antiviral agents, antibiotics, antifungal agents, preservatives or bactericides may also be added.
HK62023079234.8A 2020-04-14 2021-04-14 Solid composition for producing antibacterial, antiviral, antifungal and disinfectant solutions HK40091974A (en)

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