CN113995744B - A composition and its antibacterial application - Google Patents
A composition and its antibacterial application Download PDFInfo
- Publication number
- CN113995744B CN113995744B CN202111195294.4A CN202111195294A CN113995744B CN 113995744 B CN113995744 B CN 113995744B CN 202111195294 A CN202111195294 A CN 202111195294A CN 113995744 B CN113995744 B CN 113995744B
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- acid
- composition
- glycine
- antibacterial
- escherichia coli
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Classifications
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Abstract
Description
技术领域technical field
本发明涉及医药技术领域,尤其涉及一种组合物及其抗菌应用。The invention relates to the technical field of medicine, in particular to a composition and its antibacterial application.
背景技术Background technique
宋代陈自明所著《妇人良方》中的“仙方活命饮”内使用穿山甲,全方功效包含清热解毒,消肿溃坚,活血止痛等疮疡肿毒初起,局部红肿热痛病症。明代李时珍的《本草纲目》记载穿山甲“除痰疟寒热,风痹强直疼痛,通经脉,消痛肿,排脓血,通窍杀虫。”其“附方”中提到“下痢里急”,穿山甲、蛤粉等分,同炒研末。从以上古代医书的记载中能够看到,穿山甲被用来治疗一些现代医学认为由细菌感染引起的疾病。郭毅等在《湖南中医学院学报》上报道穿山甲水煎液对大肠杆菌等11种细菌均具有抗菌作用,其中,水煎液的主要成分为鳞甲片。Pangolin is used in the "Xianfang Huomingyin" in "Women's Prescription" written by Chen Ziming in the Song Dynasty. The effects of the whole prescription include clearing away heat and detoxification, reducing swelling and ulceration, promoting blood circulation and relieving pain, etc., and local redness, swelling, heat and pain. . Li Shizhen's "Compendium of Materia Medica" in the Ming Dynasty records that pangolins "eliminate phlegm, malaria, cold and heat, wind numbness, stiffness and pain, open the meridians, relieve pain and swelling, expel pus and blood, clear the orifices and kill insects." Divide pangolin and clam powder into equal parts, stir fry and grind into powder. From the above records in ancient medical books, we can see that pangolins are used to treat some diseases that modern medicine believes are caused by bacterial infections. Guo Yi et al reported in the "Journal of Hunan University of Traditional Chinese Medicine" that pangolin decoction has antibacterial effect on 11 kinds of bacteria including Escherichia coli, and the main component of pangolin decoction is squamous scales.
但由于现代社会中穿山甲以处于极度濒危状态,8种穿山甲均已被列入《世界自然保护联盟》(IUCN)2014年濒危物种红色名录,2016年被列入《华盛顿公约》CITES附录Ⅰ级保护动物,禁止全球贸易。而我国是《濒危野生动植物物种国际贸易公约》(CITES)的缔约国。同时,2020年,《中国药典》将穿山甲排除入药。因此,本发明通过探究穿山甲鳞片中对菌群起抑制作用的成分或成分组合物,以此进行人工合成作为替代品,在保证替换了穿山甲成分的相关治疗方案不受影响的同时还能够保护濒危动物穿山甲。However, because pangolins are extremely endangered in modern society, eight species of pangolins have been included in the 2014 Red List of Endangered Species by the International Union for Conservation of Nature (IUCN), and in 2016 they were included in the CITES Appendix I protection of the Washington Convention. Animals, global trade banned. my country is a party to the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). At the same time, in 2020, the "Chinese Pharmacopoeia" will exclude pangolins from being used as medicine. Therefore, the present invention explores the ingredients or composition of ingredients in pangolin scales that inhibit the flora, and artificially synthesizes them as a substitute, so as to ensure that the relevant treatment plan that replaces the ingredients of the pangolin is not affected, and at the same time it can protect endangered species. Animal pangolin.
在现有技术中,有机酸作为一种有机酸添加剂在各个领域中使用,其中柠檬酸作为使用频次最高的有机酸用于防腐和风味添加。公开号为CN108670897B的中国专利涉及到一种高效抑菌湿巾组合物及其制备方法。所述高效抑菌湿巾组合物的制备原料,以重量份计,包括乙醇1~6、丁二醇0.5~3、增溶剂0.2~0.6、薄荷醇0.01~0.02、香精0.1~0.12、茶叶提取物0.5~1.0、油橄榄叶提取物0.5~1.0、纳米银、马齿苋提取物0.5~1.0、柠檬酸0.1~0.2、柠檬酸钠0.05~0.15、苯氧乙醇0.01~0.05。该组合物的成分涉及了有机酸柠檬酸,并以此作为抑菌的成分,其中苯氧乙醇用于柠檬酸的助溶。然而,现存的有机酸多种多样,柠檬酸的抑菌效果在其中无法达到最高的抑菌效率。In the prior art, organic acid is used as an organic acid additive in various fields, among which citric acid is the most frequently used organic acid for antisepsis and flavor addition. The Chinese patent with publication number CN108670897B relates to a high-efficiency antibacterial wet tissue composition and a preparation method thereof. The raw materials for the preparation of the high-efficiency antibacterial wet tissue composition include, in parts by weight, 1-6 ethanol, 0.5-3 butanediol, 0.2-0.6 solubilizer, 0.01-0.02 menthol, 0.1-0.12 essence, and tea extract 0.5 to 1.0, olive leaf extract 0.5 to 1.0, nano silver, purslane extract 0.5 to 1.0, citric acid 0.1 to 0.2, sodium citrate 0.05 to 0.15, phenoxyethanol 0.01 to 0.05. The component of the composition involves the organic acid citric acid, and uses it as an antibacterial component, wherein phenoxyethanol is used for the solubilization of the citric acid. However, the existing organic acids are various, and the antibacterial effect of citric acid cannot reach the highest antibacterial efficiency among them.
公开号为CN108904374A的中国专利涉及到一种口腔清洁剂,按照重量份数包括:茶提取物3-8份,柿涩1-3份,果糖1-2份,柠檬酸2-4份,香料1-3份。The Chinese patent with the publication number CN108904374A relates to an oral cleanser, which includes: 3-8 parts by weight of tea extract, 1-3 parts of persimmon astringent, 1-2 parts of fructose, 2-4 parts of citric acid, spices 1-3 servings.
一般来说漱口水或其他口腔清洁剂的PH值要在6.5-7.5范围内,该范围的PH值偏向中性,在中性的环境下,漱口水的使用不会破坏口腔内部的蛋白质,而且能起到很好的杀菌作用。由甘氨酸构成的甘氨酸缓冲液能够保持液体处于2.2-10.6范围内。绿脓杆菌和粘质沙雷菌是一种令免疫受损的机会性感染病原,多出现于伤口处。口腔清洁剂以对口腔内的绿脓杆菌和粘质沙雷菌形成繁殖抑制的作用防止绿脓杆菌和粘质沙雷菌进入呼吸道中对患者造成伤害。Generally speaking, the pH value of mouthwash or other oral cleaning agents should be in the range of 6.5-7.5, and the pH value of this range tends to be neutral. In a neutral environment, the use of mouthwash will not destroy the protein in the oral cavity, and Can play a very good bactericidal effect. Glycine buffer consisting of glycine is able to maintain liquid in the range of 2.2-10.6. Pseudomonas aeruginosa and Serratia marcescens are immunocompromised opportunistic pathogens that frequently occur in wounds. The oral cleanser prevents Pseudomonas aeruginosa and Serratia marcescens from entering the respiratory tract and causing harm to patients by inhibiting the growth of Pseudomonas aeruginosa and Serratia marcescens in the oral cavity.
在现有技术中,多种弱酸性的抑菌防腐效果得到证实,但针对对人体疾病影响最广泛和频次最高的大肠杆菌和金黄色葡萄球菌的抑制作用的有机酸的施用并未被发现。In the prior art, the antibacterial and antiseptic effects of various weak acids have been confirmed, but the application of organic acids targeting the inhibition of Escherichia coli and Staphylococcus aureus, which have the most extensive and frequent impact on human diseases, has not been found.
本实验通过对具有良好抑菌效果的穿山甲鳞片的成分研究,探究穿山甲鳞片中的用于抑菌的代谢物组成,从而实现多组合弱酸替代穿山甲鳞片的抑菌作用。In this experiment, through the study of the composition of pangolin scales with good antibacterial effect, the composition of metabolites used for antibacterial in pangolin scales was explored, so as to realize the antibacterial effect of multi-combination weak acids instead of pangolin scales.
此外,一方面由于对本领域技术人员的理解存在差异;另一方面由于申请人做出本发明时研究了大量文献和专利,但篇幅所限并未详细罗列所有的细节与内容,然而这绝非本发明不具备这些现有技术的特征,相反本发明已经具备现有技术的所有特征,而且申请人保留在背景技术中增加相关现有技术之权利。In addition, on the one hand, due to differences in the understanding of those skilled in the art; The present invention does not possess the characteristics of these prior art, on the contrary, the present invention already possesses all the characteristics of the prior art, and the applicant reserves the right to add relevant prior art to the background technology.
发明内容Contents of the invention
针对现有技术之不足,本发明提供了一种组合物。用于人体或人体所处的环境,能够降低所述环境中存在的微生物的繁殖趋势。组合物包含:苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种。Aiming at the deficiencies of the prior art, the invention provides a composition. When used on the human body or the environment in which the human body is located, it can reduce the reproduction tendency of the microorganisms present in said environment. The composition comprises: one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid.
优选地,组合物中的成分包含:(1)苹果酸;(2)马尿酸;(3)以下任选地至少一组弱酸性成分:1)甘氨酸;2)琥珀酸和/或L-缬氨酸。Preferably, the ingredients in the composition comprise: (1) malic acid; (2) hippuric acid; (3) optionally at least one of the following weakly acidic ingredients: 1) glycine; 2) succinic acid and/or L-valeric acid acid.
优选地,组合物中的成分包含:(1)苹果酸;(2)马尿酸;(3)以下任选地至少一组弱酸性成分:1)富马酸和/或甘氨酸;2)琥珀酸和/或L-缬氨酸。Preferably, the ingredients in the composition comprise: (1) malic acid; (2) hippuric acid; (3) optionally at least one of the following weakly acidic ingredients: 1) fumaric acid and/or glycine; 2) succinic acid and/or L-valine.
根据一种优选实施方式,由苹果酸、马尿酸、琥珀酸、L-缬氨酸构成的第一成分,并与由富马酸或琥珀酸构成的第二成分共同配比形成能够对微生物生长达到抑制效果的组合物。According to a preferred embodiment, the first component composed of malic acid, hippuric acid, succinic acid, and L-valine is formulated together with the second component composed of fumaric acid or succinic acid to form a Compositions to achieve an inhibitory effect.
本技术方案的优点:相较于单一的有机酸的施用,多重组合形成的有机酸组合能够以相较单一有机酸形成更好的抑菌效果(通过抑菌试验已证实),并通过多种有机酸的组合形成不同的适用于食品、美妆、口腔清洁等作用于人体的消毒成分的风味,达到除臭清爽的目的。有机酸的形成和分解对人体无害且对环境同样无害,其抑菌杀菌的原理是以小分子形式进入细菌体内,并破坏细菌体内的碱性活性环境,从而抑制细菌活性。多种组合的有机酸的组合彼此间形成共价结构,并形成彼此增幅的抑菌效果,以较小剂量的组合物替代单性或多性随机组合的且需要大剂量添加的有机酸,从而减少食品添加剂过量摄入对人体带来的危害。The advantage of this technical solution: compared with the application of a single organic acid, the combination of organic acids formed by multiple combinations can form a better bacteriostatic effect than a single organic acid (confirmed by bacteriostatic tests), and through a variety of The combination of organic acids forms different flavors of disinfectant ingredients that are suitable for food, cosmetics, oral cleaning, etc. to act on the human body, achieving the purpose of deodorization and refreshing. The formation and decomposition of organic acids are harmless to the human body and the environment. The principle of antibacterial and sterilizing is to enter the bacteria in the form of small molecules and destroy the alkaline active environment in the bacteria, thereby inhibiting the activity of the bacteria. The combination of organic acids of multiple combinations forms a covalent structure with each other, and forms a mutual augmented bacteriostatic effect, and replaces the organic acids that are randomly combined in a single or polymorphic way and require a large dose of addition with a smaller dose of the composition, thereby Reduce the harm of excessive intake of food additives to the human body.
根据一种优选实施方式,作用于人体或环境的所述组合物包含苹果酸、马尿酸、甘氨酸和柠檬酸,其中,组合物基于苹果酸和柠檬酸的相互作用能够以缓冲酸性感官的方式增强用于作用于环境的果香成分。According to a preferred embodiment, said composition acting on the human body or the environment comprises malic acid, hippuric acid, glycine and citric acid, wherein the composition is based on the interaction of malic acid and citric acid being able to enhance the buffering of acidic senses For fruity ingredients that act on the environment.
根据一种优选实施方式,组合物至少包含苹果酸、马尿酸、甘氨酸和柠檬酸,其中,构成所述组合物的组分以非牛顿流体的形式施用于皮肤表面。According to a preferred embodiment, the composition comprises at least malic acid, hippuric acid, glycine and citric acid, wherein the components constituting the composition are applied to the skin surface in the form of a non-Newtonian fluid.
根据一种优选实施方式,所述组合物至少包含苹果酸、马尿酸、甘氨酸和富马酸,其中,构成所述组合物的组分以非牛顿流体的形式施用于皮肤表面。According to a preferred embodiment, the composition comprises at least malic acid, hippuric acid, glycine and fumaric acid, wherein the components constituting the composition are applied to the skin surface in the form of a non-Newtonian fluid.
本技术方案的优点:用于皮肤表面的修复、治疗或保护的药品、化妆品在涂抹过程中由于流体的流动性而在脸部无法达到稳定的挂接,但膏状的药品形态由于粘稠性不容易均匀涂抹。本发明采用非牛顿流体的组分形式,降低其流动性,并不改变粘稠度,从而保证组分在脸部及皮肤位置扒附的稳定性。The advantages of this technical solution: the drugs and cosmetics used for the repair, treatment or protection of the skin surface cannot achieve stable attachment on the face due to the fluidity of the fluid during the application process, but the paste drug form is due to the viscosity Not easy to apply evenly. The present invention adopts the component form of non-Newtonian fluid, which reduces its fluidity and does not change the viscosity, thereby ensuring the stability of the components on the face and skin.
根据一种优选实施方式,组合物能够以协同作用的方式抑制大肠杆菌和金黄色葡萄球菌的分裂。According to a preferred embodiment, the composition can inhibit the division of Escherichia coli and Staphylococcus aureus in a synergistic manner.
一种组合物,其能够以分散相的形式与摩擦剂构成口腔清洁剂的清洁成分,组合物用于对口腔内部的大肠杆菌和金黄色葡萄球菌的生长进行抑制,其中,组合物包含苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种。A composition, which can constitute a cleaning component of an oral cleaning agent in the form of a dispersed phase and an abrasive, and the composition is used to inhibit the growth of Escherichia coli and Staphylococcus aureus in the oral cavity, wherein the composition contains malic acid , hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid in one or more.
一种组合物,其能够对人体皮肤表面或食品中的大肠杆菌和金黄色葡萄球菌的繁衍起到抑制作用,其中,组合物包含苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种。A composition capable of inhibiting the propagation of Escherichia coli and Staphylococcus aureus on the surface of human skin or in food, wherein the composition contains malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L - One or more of valine and citric acid.
一种组合物的抗菌应用,该组合物作为添加剂在洗涤剂或杀菌剂中施用,作为添加剂的所述组合物设置有用于释放H+的第一组合物和用于增加消杀效果和时间的第二组合物。第一组合物包含:苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种,第二组合物包含水胶体。其中,在作为添加剂的所述组合物施用时所述第一组合物介入所述第二组合物,并伴随所述第二组合物对洗涤剂或杀菌剂施用的目标携带的大肠杆菌或金黄色葡萄球菌的包裹而作用于大肠杆菌或金黄色葡萄球菌的菌体内部。Antibacterial application of a composition, which is applied as an additive in a detergent or a bactericide, said composition as an additive is provided with a first composition for releasing H + and for increasing the killing effect and time second composition. The first composition includes: one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid, and the second composition includes hydrocolloid. Wherein, when the composition as an additive is applied, the first composition intervenes in the second composition, and accompanied by the second composition on the E. Staphylococcus encapsulation acts on the inside of Escherichia coli or Staphylococcus aureus.
一种组合物的抗菌应用,其特征在于,用于细菌性感染引起的组织炎症中的细菌的生长抑制药物,所述药物的主要成分包含:苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种。An antibacterial application of a composition, characterized in that it is used as a drug for inhibiting the growth of bacteria in tissue inflammation caused by bacterial infection, and the main components of the drug include: malic acid, hippuric acid, fumaric acid, glycine, succinic acid One or more of acid, L-valine and citric acid.
具体实施方式Detailed ways
下面结合附图进行详细说明。A detailed description will be given below in conjunction with the accompanying drawings.
本发明设计一种抑菌组合物,其能够对以大肠杆菌和金黄色葡萄球菌为代表的微生物实现最有效果的抑制作用。The invention designs an antibacterial composition, which can realize the most effective inhibition on microorganisms represented by Escherichia coli and Staphylococcus aureus.
用于抑菌的有机酸包含富马酸(Fumaric acid)、琥珀酸(Succinic acid)、L-缬氨酸(L-Valine)、苹果酸(Malic acid)、柠檬酸(Citric acid)、甘氨酸(Glycine)和马尿酸(Hippuric acid)。其比例与穿山甲鳞片中含量一致,其中,在总提取液(CV)中,富马酸占比0.1%、琥珀酸占比0.4%、L-缬氨酸占比1.3%、苹果酸占比1.2%、柠檬酸占比0.2%、甘氨酸占比0.1%和马尿酸占比0.3%。优选的,上述比例是可以调整的,也是有效的。Organic acids used for antibacterial include fumaric acid, succinic acid, L-valine, malic acid, citric acid, glycine ( Glycine) and hippuric acid (Hippuric acid). Its ratio is consistent with the content in pangolin scales. Among them, in the total extract (CV), fumaric acid accounts for 0.1%, succinic acid accounts for 0.4%, L-valine accounts for 1.3%, and malic acid accounts for 1.2%. %, citric acid accounted for 0.2%, glycine accounted for 0.1% and hippuric acid accounted for 0.3%. Preferably, the above ratio is adjustable and effective.
本文中涉及的微生物能够包含革兰氏阴性菌、革兰氏阳性菌,或包含以金黄色葡萄球菌为致病葡萄球菌的代表,以大肠杆菌为代表的条件致病菌或其他致病细菌,如结核杆菌。The microorganisms involved in this paper can include Gram-negative bacteria, Gram-positive bacteria, or include Staphylococcus aureus as the representative of pathogenic Staphylococcus, Escherichia coli as the representative of conditional pathogenic bacteria or other pathogenic bacteria, Such as Mycobacterium tuberculosis.
本发明中用于实验和构成组合物成分的有机酸均为人工合成的有机酸。The organic acids used in the experiments and composition components of the present invention are all synthetic organic acids.
通过该类组合物悬殊性含量配比,从而达到相较同体积的单一或少组合物的更优抑菌的效果。Through the disparate content ratio of such compositions, a better antibacterial effect can be achieved compared with a single or less composition of the same volume.
实施例1Example 1
基于最小抑菌浓度法(MIC)进行抑菌试验,分别将上述抗菌代谢物用于大肠杆菌(E.coli;Escherichia coli)和金黄色葡萄球菌(S.aureus;Staphylococcus aureus)、绿脓杆菌(P.aeruginosa;Pseudomonas aeruginosa)和粘质沙雷菌(S.marcescens;Serratiamarcescens)的最小抑菌浓度(MIC;Minimum Inhibitory Concentration)检测。Antibacterial tests were carried out based on the minimum inhibitory concentration method (MIC), and the above antibacterial metabolites were used for Escherichia coli (E. The minimum inhibitory concentration (MIC; Minimum Inhibitory Concentration) detection of P.aeruginosa; Pseudomonas aeruginosa) and Serratia marcescens (S.marcescens; Serratiamarcescens).
(1)实验材料:(1) Experimental materials:
1)培养基1) culture medium
采用溶菌肉汤(LB;Lysogeny Broth)培养基,含10g/L蛋白胨,5g/L酵母提取物和10g/L氯化钠。Lysogeny Broth (LB; Lysogeny Broth) medium containing 10 g/L peptone, 5 g/L yeast extract and 10 g/L sodium chloride was used.
2)抗菌药物:2) Antibacterial drugs:
包含富马酸、琥珀酸、L-缬氨酸、苹果酸、柠檬酸、甘氨酸和马尿酸中的一种或几种构成的全部组合物。The whole composition comprises one or more of fumaric acid, succinic acid, L-valine, malic acid, citric acid, glycine and hippuric acid.
(2)抑菌试验步骤如下:(2) The steps of antibacterial test are as follows:
1)菌悬液制备1) Preparation of bacterial suspension
将保存的代表革兰氏阴性菌的大肠杆菌和代表革兰氏阳性菌的金黄色葡萄球菌同时复苏。用接种环在已分纯的待测菌平板上,挑取单个直径约1mm的菌落,接种于2mL LB肉汤中,于37℃的生化培养箱中进行培养。增菌后的对数生长期菌液用LB肉汤校正浓度至0.5麦氏比浊标准(即625nm处吸光度为0.08~0.10),约含1×108~2×108CFU·mL-1。The preserved Escherichia coli representing Gram-negative bacteria and Staphylococcus aureus representing Gram-positive bacteria were resuscitated simultaneously. Use an inoculation loop to pick a single colony with a diameter of about 1mm on the plate of the purified bacteria to be tested, inoculate it in 2mL LB broth, and culture it in a biochemical incubator at 37°C. After enrichment, use LB broth to correct the concentration of the bacteria solution in the logarithmic growth phase to 0.5 McFarland turbidimetric standard (that is, the absorbance at 625nm is 0.08-0.10), containing about 1×10 8 to 2×10 8 CFU·mL -1 .
2)抗菌药物制备2) Preparation of antibacterial drugs
采用二倍稀释法制备浓度为4C、2C、C、0.5C、0.25C、0.125C、0.0625C、0.03125C的组合抗菌药物,取无菌试管8支依次编号,在2-8支试管中加入1ml无菌水。在第一个试管中配制2ml 4C的抗菌药物,取1ml第一支试管中的溶液加入第二支试管,混匀后,再取1ml第二支试管中的溶液加入到第三支试管,依次稀释。Prepare combined antibacterial drugs with concentrations of 4C, 2C, C, 0.5C, 0.25C, 0.125C, 0.0625C, and 0.03125C by double dilution method, take 8 sterile test tubes and number them in sequence, and add them to 2-8 test tubes 1ml sterile water. Prepare 2ml of 4C antibacterial drug in the first test tube, take 1ml of the solution in the first test tube and add it to the second test tube, after mixing, take 1ml of the solution in the second test tube and add it to the third test tube, and then dilution.
3)MIC测定3) MIC determination
在96孔板的第1列加入200μL LB肉汤培养基作阴性对照,第2-10列中加入180μL制备好的菌悬液至终浓度为1×105CFU·mL-1。第2列加入20μL无菌水作为阳性对照组,第3~10列分别加入20μL药物浓度终浓度依次为0.4、0.2、0.1、0.05、0.025、0.0125、0.00625和0.003125C。将分别接种好的药敏板置于37℃温箱中培养24h,通过观察LB肉汤培养基的浊度并检测OD值来检测MIC值,实验重复3次。Add 200 μL of LB broth medium to column 1 of the 96-well plate as a negative control, and add 180 μL of prepared bacterial suspension to column 2-10 to a final concentration of 1×10 5 CFU·mL -1 . Add 20 μL of sterile water to column 2 as a positive control group, and add 20 μL of drug concentration to columns 3 to 10. The final concentrations are 0.4, 0.2, 0.1, 0.05, 0.025, 0.0125, 0.00625 and 0.003125C. The respectively inoculated drug-sensitivity plates were placed in a 37°C incubator and incubated for 24 hours. The MIC value was detected by observing the turbidity of the LB broth medium and detecting the OD value. The experiment was repeated 3 times.
得到结果如表1中各个代谢物对大肠杆菌和金黄色葡萄菌的最小抑制浓度,独立存在的集中抗菌代谢物汇总,对于大肠杆菌和金黄色葡萄球菌抑制效果最好的是苹果酸。The results obtained are shown in Table 1 as the minimum inhibitory concentration of each metabolite to Escherichia coli and Staphylococcus aureus, and the summary of independent concentrated antibacterial metabolites. The best inhibitory effect on Escherichia coli and Staphylococcus aureus is malic acid.
表1Table 1
为了验证苹果酸及其组合物形成的最优效果,本实验进一步将苹果酸与其他代谢物作为组合物进行抑菌试验,得到以MIC值为代表的结果如表2所示。In order to verify the optimal effect of malic acid and its composition, this experiment further used malic acid and other metabolites as a composition to conduct antibacterial tests, and the results represented by MIC values are shown in Table 2.
表2Table 2
实验结果显示,添加了苹果酸的双成分组合物对大肠杆菌和金黄色葡萄球菌的MIC值变小,表明其对大肠杆菌和金黄色葡萄球菌具有更高的抑制效果。再进一步,进行三种组合物的随机分配,并进行抑菌试验,如表3所示。The experimental results showed that the MIC value of the two-component composition added with malic acid on Escherichia coli and Staphylococcus aureus became smaller, indicating that it had a higher inhibitory effect on Escherichia coli and Staphylococcus aureus. Further, the random distribution of the three compositions was carried out, and the antibacterial test was carried out, as shown in Table 3.
表3table 3
苹果酸和富马酸的组合物在与L-缬氨酸或柠檬酸组合时抑菌效果回弹变弱,同样的,苹果酸和L-缬氨酸在与甘氨酸或马尿酸组合时结果相同,对大肠杆菌和金黄色葡萄球菌的抑制效果减弱,MIC值回升至0.4C。苹果酸、马尿酸和柠檬酸形成的组合物对大肠杆菌的抑制效果达到最优,MIC值为0.1C。The combination of malic acid and fumaric acid has weak antibacterial effect when combined with L-valine or citric acid. Similarly, malic acid and L-valine have the same results when combined with glycine or hippuric acid , the inhibitory effect on Escherichia coli and Staphylococcus aureus weakened, and the MIC value rose back to 0.4C. The combination of malic acid, hippuric acid and citric acid has the best inhibitory effect on Escherichia coli, with an MIC value of 0.1C.
本实验还对选择苹果酸作为主要成分,通过分配其他代谢物与苹果酸构成四种组合物进行抑菌试验,结果如表4所示。In this experiment, malic acid was selected as the main component, and four compositions were formed by assigning other metabolites and malic acid to conduct antibacterial tests. The results are shown in Table 4.
表4Table 4
结果显示,苹果酸、富马酸、甘氨酸和马尿酸的组合物以及苹果酸、柠檬酸、甘氨酸和马尿酸的组合物能够形成MIC低至0.1C的抑菌效果。The results showed that the composition of malic acid, fumaric acid, glycine and hippuric acid and the composition of malic acid, citric acid, glycine and hippuric acid can form the antibacterial effect with MIC as low as 0.1C.
本实验还对选择苹果酸作为主要成分,通过分配其他代谢物与苹果酸构成五种组合物进行抑菌试验,结果如表5所示。In this experiment, malic acid was selected as the main component, and five compositions composed of other metabolites and malic acid were selected for antibacterial test. The results are shown in Table 5.
表5table 5
结果显示,苹果酸、L-缬氨酸、柠檬酸、甘氨酸、马尿酸;苹果酸、富马酸、琥珀酸、L-缬氨酸、马尿酸;苹果酸、富马酸、L-缬氨酸、甘氨酸、马尿酸三种组合物能够对大肠杆菌形成MIC值0.1C的抑菌效果。而组合物苹果酸、琥珀酸、L-缬氨酸、甘氨酸、马尿酸;苹果酸、富马酸、L-缬氨酸、柠檬酸、马尿酸;苹果酸、富马酸、柠檬酸、甘氨酸、马尿酸;苹果酸、琥珀酸、L-缬氨酸、柠檬酸、马尿酸;苹果酸、琥珀酸、柠檬酸、甘氨酸、马尿酸中任一组能够对大肠杆菌和金黄色葡萄球菌形成MIC值0.1C的抑菌效果。相较于现有技术中使用单一有机酸或两项有机酸作为添加剂,其抑菌效果达不到四种以上有机酸组合形成的抑菌添加剂。The results showed that malic acid, L-valine, citric acid, glycine, hippuric acid; malic acid, fumaric acid, succinic acid, L-valine, hippuric acid; malic acid, fumaric acid, L-valine The three compositions of acid, glycine and hippuric acid can form a bacteriostatic effect on Escherichia coli with an MIC value of 0.1C. And the composition malic acid, succinic acid, L-valine, glycine, hippuric acid; malic acid, fumaric acid, L-valine, citric acid, hippuric acid; malic acid, fumaric acid, citric acid, glycine , hippuric acid; malic acid, succinic acid, L-valine, citric acid, hippuric acid; any group of malic acid, succinic acid, citric acid, glycine, hippuric acid can form MIC against Escherichia coli and Staphylococcus aureus Bacteriostatic effect with a value of 0.1C. Compared with the use of a single organic acid or two organic acids as additives in the prior art, its antibacterial effect is not as good as the antibacterial additive formed by combining more than four organic acids.
本实验还对选择苹果酸作为主要成分,通过分配其他代谢物与苹果酸构成六种组合物、七种代谢物混合进行抑菌试验,结果如表6所示。In this experiment, malic acid was selected as the main component, and six compositions and seven metabolites were mixed by assigning other metabolites and malic acid to conduct antibacterial tests. The results are shown in Table 6.
表6Table 6
结果显示,即使是六种及以上的代谢物混合,其对金黄色葡萄球菌和大肠杆菌的抑菌效果能够达到MIC值0.1C。The results showed that even if six or more metabolites were mixed, their antibacterial effect on Staphylococcus aureus and Escherichia coli could reach MIC value of 0.1C.
进一步,以大肠杆菌、金属葡萄球菌、绿脓杆菌和粘质沙雷菌为例,对包含苹果酸、马尿酸、富马酸和甘氨酸的代谢物组合进行试验,结果如表7所示:Further, taking Escherichia coli, Staphylococcus metallobacter, Pseudomonas aeruginosa and Serratia marcescens as examples, the metabolite combination containing malic acid, hippuric acid, fumaric acid and glycine was tested, and the results are shown in Table 7:
表7Table 7
结果显示,由苹果酸、马尿酸、富马酸和甘氨酸构成的有机酸代谢物组合物对大肠杆菌和金黄色葡萄球菌的抑菌效果达到MIC值0.1C,对绿脓杆菌和粘质沙雷菌的抑菌效果达到MIC值0.2C。由苹果酸、马尿酸、富马酸和甘氨酸构成的有机酸代谢物组合物对以大肠杆菌、金属葡萄球菌、绿脓杆菌和粘质沙雷菌为代表的细菌,尤其是致病菌,具有对其生长的抑制作用。The results showed that the organic acid metabolite composition composed of malic acid, hippuric acid, fumaric acid and glycine had an antibacterial effect on Escherichia coli and Staphylococcus aureus reaching an MIC value of 0.1C, The antibacterial effect of bacteria reached MIC value 0.2C. The organic acid metabolite composition composed of malic acid, hippuric acid, fumaric acid and glycine has antibacterial properties against bacteria represented by Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Serratia marcescens, especially pathogenic bacteria inhibition of its growth.
粘质沙雷菌为细菌最小者,属革兰氏阴性杆菌,为条件致病菌。Serratia marcescens is the smallest bacterium, a Gram-negative bacillus, and an opportunistic pathogen.
绿脓杆菌是一种革兰氏阴性菌,为机会性感染细菌。Pseudomonas aeruginosa is a gram-negative bacterium that is an opportunistic infection.
大肠杆菌、金属葡萄球菌、绿脓杆菌和粘质沙雷菌广泛分布于自然界中,其能够通过人体口鼻等位置进入人体,在一定条件或环境状态下引起人体产生炎症等致病反应。因此,本实验选用上述四种菌种作为抑菌试验的试验对象。Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Serratia marcescens are widely distributed in nature. They can enter the human body through the mouth and nose of the human body, and cause inflammation and other pathogenic reactions in the human body under certain conditions or environmental conditions. Therefore, in this experiment, the above four strains were selected as the test objects of the antibacterial test.
基于上述实验结果,苹果酸、甘氨酸和马尿酸构成的组合物能够与柠檬酸或富马酸形成对金黄色葡萄球菌和大肠杆菌的抑菌效果达到MIC值0.1C的效果。Based on the above experimental results, the composition composed of malic acid, glycine and hippuric acid can be combined with citric acid or fumaric acid to form an antibacterial effect on Staphylococcus aureus and Escherichia coli with an MIC value of 0.1C.
上述用于实验的组合物中的配比能够为富马酸占比0.1%、琥珀酸占比0.4%、L-缬氨酸占比1.3%、苹果酸占比1.2%、柠檬酸占比0.2%、甘氨酸占比0.1%和马尿酸占比0.3%,以上述比例进行抗菌组合物配制。The proportions in the composition used in the experiment above can be 0.1% for fumaric acid, 0.4% for succinic acid, 1.3% for L-valine, 1.2% for malic acid, and 0.2% for citric acid. %, glycine accounted for 0.1% and hippuric acid accounted for 0.3%, and the antibacterial composition was prepared in the above proportions.
优选地,用于降低人体体表或人体所处环境中存在的微生物的繁殖趋势的组合物包含:0.125%~0.482%苹果酸、0.135%~0.422%L-缬氨酸、0.021%~0.081%柠檬酸、0.01%~0.04%琥珀酸、0.031%~0.121%马尿酸、0.001%~0.041%甘氨酸和0.01%~0.041%富马酸中的一种或几种。Preferably, the composition for reducing the reproduction tendency of microorganisms existing on the surface of the human body or in the environment where the human body is located comprises: 0.125%-0.482% malic acid, 0.135%-0.422% L-valine, 0.021%-0.081% One or more of citric acid, 0.01%-0.04% succinic acid, 0.031%-0.121% hippuric acid, 0.001%-0.041% glycine and 0.01%-0.041% fumaric acid.
优选地,所述组合物中各组分比例能够为:苹果酸在总组分中占比1%~30%、L-缬氨酸在总组分中占比0.1%~20%、柠檬酸在总组分中占比0.1%~20%、琥珀酸在总组分中占比0.1%~20%、马尿酸在总组分中占比0.1%~20%、甘氨酸在总组分中占比0.1%~20%和富马酸在总组分中占比0.1%~20%。Preferably, the ratio of each component in the composition can be: malic acid accounts for 1% to 30% of the total components, L-valine accounts for 0.1% to 20% of the total components, citric acid Accounting for 0.1%-20% of the total components, 0.1%-20% for succinic acid, 0.1%-20% for hippuric acid, and 0.1%-20% for glycine The ratio is 0.1% to 20% and fumaric acid accounts for 0.1% to 20% of the total components.
优选地,所述组合物中各组分比例能够为:苹果酸在总组分中占比10%~40%、L-缬氨酸在总组分中占比0.01%~10%、柠檬酸在总组分中占比0.01%~10%、琥珀酸在总组分中占比0.01%~20%、马尿酸在总组分中占比0.01%~20%、甘氨酸在总组分中占比0.01%~20%和富马酸在总组分中占比0.01%~10%。Preferably, the ratio of each component in the composition can be: malic acid accounts for 10% to 40% of the total components, L-valine accounts for 0.01% to 10% of the total components, citric acid Accounting for 0.01%-10% of the total components, 0.01%-20% for succinic acid, 0.01%-20% for hippuric acid, and 0.01%-20% for glycine The ratio is 0.01% to 20% and fumaric acid accounts for 0.01% to 10% of the total components.
优选地,所述苹果酸能够在总组分中按重量计在约0.1%至约20%、约1%至约10%、约3%至约8%、约6%至约12%、约15%至约18%、约17%至约20%、20%至60%的范围内,或按重量计为约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约15%、约20%、约30%或约40%,包括其间的所有范围和子范围。Preferably, the malic acid can range from about 0.1% to about 20%, about 1% to about 10%, about 3% to about 8%, about 6% to about 12%, about In the range of 15% to about 18%, about 17% to about 20%, 20% to 60%, or by weight about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, about 20%, about 30%, or about 40%, including all ranges and subranges therebetween.
优选地,所述L-缬氨酸能够在总组分中按重量计在约0.01%至约1%、约1%至约10%、约3%至约8%、约6%至约12%、约15%至约18%、约17%至约20%的范围内,或按重量计为约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约15%、约20%、约30%或约40%,包括其间的所有范围和子范围。Preferably, the L-valine can range from about 0.01% to about 1%, from about 1% to about 10%, from about 3% to about 8%, from about 6% to about 12% by weight in the total components. %, about 15% to about 18%, about 17% to about 20%, or about 1%, about 2%, about 3%, about 4%, about 5%, about 6% by weight, About 7%, about 8%, about 9%, about 10%, about 15%, about 20%, about 30%, or about 40%, including all ranges and subranges therebetween.
优选地,所述柠檬酸能够在总组分中按重量计在约0.01%至约2%、约1%至约10%、约3%至约8%、约6%至约12%、约15%至约18%、约17%至约20%的范围内,或按重量计为约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约15%、约20%、约30%或约40%,包括其间的所有范围和子范围。Preferably, the citric acid can range from about 0.01% to about 2%, about 1% to about 10%, about 3% to about 8%, about 6% to about 12%, about In the range of 15% to about 18%, about 17% to about 20%, or about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7% by weight , about 8%, about 9%, about 10%, about 15%, about 20%, about 30%, or about 40%, including all ranges and subranges therebetween.
优选地,所述琥珀酸能够在总组分中按重量计在约0.1%至约20%、约1%至约10%、约3%至约8%、约6%至约12%、约15%至约18%、约17%至约20%的范围内,或按重量计为约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约15%、约20%、约30%或约40%,包括其间的所有范围和子范围。Preferably, the succinic acid can range from about 0.1% to about 20%, about 1% to about 10%, about 3% to about 8%, about 6% to about 12%, about In the range of 15% to about 18%, about 17% to about 20%, or about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7% by weight , about 8%, about 9%, about 10%, about 15%, about 20%, about 30%, or about 40%, including all ranges and subranges therebetween.
优选地,所述马尿酸能够在总组分中按重量计在约0.1%至约20%、约1%至约10%、约3%至约8%、约6%至约12%、约15%至约18%、约17%至约20%、20%至60%的范围内,或按重量计为约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约15%、约20%、约30%或约40%,包括其间的所有范围和子范围。Preferably, the hippuric acid can comprise from about 0.1% to about 20%, about 1% to about 10%, about 3% to about 8%, about 6% to about 12%, about In the range of 15% to about 18%, about 17% to about 20%, 20% to 60%, or by weight about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, about 20%, about 30%, or about 40%, including all ranges and subranges therebetween.
优选地,所述甘氨酸能够在总组分中按重量计在约0.1%至约2%、约1%至约10%、约3%至约8%、约6%至约12%、约15%至约18%、约17%至约20%的范围内,或按重量计为约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约15%、约20%、约30%或约40%,包括其间的所有范围和子范围。Preferably, the glycine can range from about 0.1% to about 2%, about 1% to about 10%, about 3% to about 8%, about 6% to about 12%, about 15% by weight of the total components % to about 18%, about 17% to about 20%, or by weight about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, About 8%, about 9%, about 10%, about 15%, about 20%, about 30%, or about 40%, including all ranges and subranges therebetween.
优选地,所述富马酸能够在总组分中按重量计在约0.01%至约20%、约1%至约10%、约3%至约8%、约6%至约12%、约15%至约18%、约17%至约20%的范围内,或按重量计为约1%、约2%、约3%、约4%、约5%、约6%、约7%、约8%、约9%、约10%、约15%、约20%、约30%或约40%,包括其间的所有范围和子范围。Preferably, the fumaric acid can range from about 0.01% to about 20%, about 1% to about 10%, about 3% to about 8%, about 6% to about 12%, In the range of about 15% to about 18%, about 17% to about 20%, or about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7% by weight %, about 8%, about 9%, about 10%, about 15%, about 20%, about 30%, or about 40%, including all ranges and subranges therebetween.
优选地,苹果酸、L-缬氨酸、柠檬酸、琥珀酸、马尿酸、甘氨酸和富马酸的组合范围能够包含但不限于上述的比例和组合范围。Preferably, the combination range of malic acid, L-valine, citric acid, succinic acid, hippuric acid, glycine and fumaric acid can include but not limited to the above ratio and combination range.
对于大肠杆菌具有MIC值达到0.1C的抑制效果的组合物以苹果酸、马尿酸和柠檬酸的组合物作为代表,而同时对大肠杆菌和金黄色葡萄球菌具有MIC值达到0.1C的抑制效果的组合物以苹果酸、富马酸、甘氨酸、马尿酸;苹果酸、柠檬酸、甘氨酸、马尿酸为代表。由于上述形成组合物的成分均为弱酸性成分,且均能够作为食品添加剂被人体吸收,因此,作为对人体无害的成分,上述多组组合物能够应用于多种领域。现有技术中,使用有机酸的方法和认知为:任一有机酸均具有抑菌作用,通过法律允许的范围内大剂量的在食物或其他与人体接触的消毒液体中添加并进行抑菌即可。然而,有机酸作为添加剂在大量使用时会在身体内产生转化产物,少剂量依靠代谢,但大剂量则无法保证全部产物能够及时的代谢出体外,因此大剂量的添加剂在一定时间内会对人体身体造成危害。本发明通过对有效抑菌的有机酸进行抑菌配比,得到最优的抑菌组合物,能够通过增加可食用有机酸的种类来减少可食用有机酸的添加量,从而帮助食物或其他在保证防腐效果的同时形成对人体更健康的影响。The composition with MIC value reaching 0.1C for Escherichia coli is represented by the composition of malic acid, hippuric acid and citric acid, while the composition with MIC value reaching 0.1C for Escherichia coli and Staphylococcus aureus at the same time The composition is represented by malic acid, fumaric acid, glycine, hippuric acid; malic acid, citric acid, glycine, hippuric acid. Since the above-mentioned components forming the composition are all weakly acidic components and can be absorbed by the human body as food additives, the above-mentioned multi-group composition can be used in various fields as components that are harmless to the human body. In the prior art, the method and cognition of using organic acid is: any organic acid has antibacterial effect, and it is added in large doses within the scope permitted by law to antibacterial That's it. However, when organic acids are used as additives in large quantities, conversion products will be produced in the body. Small doses rely on metabolism, but large doses cannot guarantee that all products can be metabolized out of the body in a timely manner. bodily harm. The present invention obtains the optimal bacteriostatic composition through the bacteriostatic ratio of effective bacteriostatic organic acids, and can reduce the amount of edible organic acids by increasing the types of edible organic acids, thereby helping food or other While ensuring the antiseptic effect, it will have a healthier impact on the human body.
实施例2Example 2
本实施例是对实施例1的进一步改进,重复的内容不再赘述。This embodiment is a further improvement on Embodiment 1, and repeated content will not be repeated here.
以目前用于慢性咽炎治疗的利咽片为例。针对细菌感染产生的慢性咽炎,利咽片能够对该病症产生较好的作用。利咽片成分包含穿山甲(制)、土鳖虫、僵蚕、牡蛎(煅)、玄参,其成分中的穿山甲(制)由于取自濒危生物,该成分为禁用药品,导致利咽片无法被作为处方药或非处方药为患者治疗。本发明通过探究穿山甲鳞片中对菌群抑制,尤其是大肠杆菌和金黄色葡萄球菌的抑制作用进行探究,发现对大肠杆菌和金黄色葡萄球菌具有有效抑制作用的一组或多组组合物。药物的主要成分包含:苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种。在进行利咽片的穿山甲成分替换时,一方面替换成分能够采用相似成分的生物组织提取物,另一方面替换成分还能够是通过人工合成有效抑菌的代谢物替代品成分。优选地,替换成分使用人工合成的化合物时,其能够为本实验中设计的对以大肠杆菌为代表的革兰氏阴性菌和以金黄色葡萄球菌为代表的革兰氏阳性菌抑制效果最优之一的组合物:苹果酸、富马酸、琥珀酸、L-缬氨酸、柠檬酸和甘氨酸。上述有机酸的添加还能够为药片带来果味等受儿童欢迎的口味,从而增加婴幼儿服药的积极性。Take the Liyan Tablet currently used in the treatment of chronic pharyngitis as an example. For chronic pharyngitis caused by bacterial infection, Liyan Tablets can have a better effect on the disease. The ingredients of Liyan Tablets include pangolin (manufactured), wood beetle, silkworm, oyster (calcined), and scrophulariaceae. The pangolin (made) in the ingredients is taken from endangered organisms. This ingredient is a banned drug, so Liyan Tablets cannot be used. Treat patients as prescription or over-the-counter medicines. The present invention explores the inhibitory effect on bacterial flora in pangolin scales, especially Escherichia coli and Staphylococcus aureus, and finds one or more groups of compositions that have effective inhibitory effects on Escherichia coli and Staphylococcus aureus. The main components of the medicine include: one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid. When replacing pangolin ingredients in Liyan Tablets, on the one hand, the replacement ingredients can use biological tissue extracts with similar ingredients, and on the other hand, the replacement ingredients can also be artificially synthesized effective antibacterial metabolite substitute ingredients. Preferably, when the synthetic compound is used as the replacement component, it can have the best inhibitory effect on Gram-negative bacteria represented by Escherichia coli and Gram-positive bacteria represented by Staphylococcus aureus designed in this experiment One of the compositions: malic acid, fumaric acid, succinic acid, L-valine, citric acid and glycine. The addition of the above-mentioned organic acid can also bring fruity and other flavors popular to children to the tablet, thereby increasing the enthusiasm of infants and young children to take medicine.
实施例3Example 3
本实施例是对实施例1或实施例2的进一步改进,重复的内容不再赘述。This embodiment is a further improvement on Embodiment 1 or Embodiment 2, and repeated content will not be repeated here.
组合物还是用于各种食品中作为添加剂组合物,有效抑制食品中的大肠杆菌和金黄色葡萄球菌。例如,在一些天然果汁中添加,即通过苹果酸和柠檬酸的配比增加天然风味,又配合果汁在真空或密封包装通过抑制大肠杆菌和金黄色葡萄球菌的生长而实现防腐效果。添加剂的主要成分包含:苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种。苹果酸和柠檬酸分别存在或组合作用会形成具有水果风味的添加剂。The composition is also used in various foods as an additive composition to effectively inhibit Escherichia coli and Staphylococcus aureus in foods. For example, adding it to some natural fruit juices increases the natural flavor through the ratio of malic acid and citric acid, and cooperates with the fruit juice in vacuum or sealed packaging to achieve antiseptic effect by inhibiting the growth of Escherichia coli and Staphylococcus aureus. The main components of the additive include: one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid. Malic acid and citric acid alone or in combination form an additive with a fruity flavor.
实施例4Example 4
本实施例是对实施例1、实施例2或实施例3的进一步改进,重复的内容不再赘述。This embodiment is a further improvement on Embodiment 1, Embodiment 2 or Embodiment 3, and repeated content will not be repeated.
组合物还能够用于家庭或对一般生活条件下的细菌消杀。例如,在家居生活中,需要对环境进行抑菌细菌维护或对衣物进行抑菌清洗,尤其是对人体有害的金黄色葡萄球菌。酒精或84消毒液的消杀对人体同样具有损伤,且不适合有孕妇或儿童的家庭使用。本发明能够基于该弱酸性成分的组合物,并配合其他无危害消杀细菌的成分形成适用于有儿童或孕妇的家庭的消杀细菌的液体试剂。The composition can also be used in households or to disinfect bacteria under normal living conditions. For example, in home life, it is necessary to maintain antibacterial bacteria in the environment or clean clothes antibacterially, especially Staphylococcus aureus, which is harmful to the human body. The disinfection of alcohol or 84 disinfectant is also harmful to the human body, and it is not suitable for families with pregnant women or children. The present invention can form a liquid reagent for disinfecting bacteria suitable for families with children or pregnant women based on the composition of the weakly acidic component and other harmless bacteria-killing components.
有机酸构成的组合物能够作为添加剂在洗涤剂或杀菌剂中施用。作为添加剂的组合物用于衣物或环境抑菌除臭。组合物设置有包含作为PH调节剂的第一组合物和用于增加消杀效果和时间的第二组合物。第一组合物包含两种组合中的任意一种:苹果酸、甘氨酸、马尿酸、柠檬酸;苹果酸、甘氨酸、马尿酸、富马酸。第二组合物包含水胶体。Compositions composed of organic acids can be used as additives in detergents or bactericides. The composition as an additive is used for antibacterial and deodorizing of clothes or environment. The composition is provided with a first composition as a pH regulator and a second composition for increasing the disinfecting effect and time. The first composition comprises any one of two combinations: malic acid, glycine, hippuric acid, citric acid; malic acid, glycine, hippuric acid, fumaric acid. The second composition comprises a hydrocolloid.
包含多糖和蛋白质的水胶体形成凝胶网络。在由凝胶网络包裹洗涤剂或杀菌剂施用的目标携带的大肠杆菌或金黄色葡萄球菌时,存在于水胶体中的第一组合物基于凝胶网络对菌体的压力而自菌体进入菌体内部,第一组合物和第二组合物共同作用形成具有协同作用的有机酸,在菌体内部释放H+,破坏菌体内部碱性环境,从而抑制菌体活性。第一组合物介入水胶体,并伴随水胶体对洗涤剂或杀菌剂施用的目标携带的大肠杆菌或金黄色葡萄球菌的包裹而作用于大肠杆菌或金黄色葡萄球菌的菌体内部。Hydrocolloids comprising polysaccharides and proteins form a gel network. When the Escherichia coli or Staphylococcus aureus carried by the target of detergent or bactericide application is wrapped by the gel network, the first composition present in the hydrocolloid enters the bacterial cell from the cell based on the pressure of the gel network on the cell. Inside the cell, the first composition and the second composition work together to form a synergistic organic acid, release H + inside the cell, destroy the alkaline environment inside the cell, and thereby inhibit the activity of the cell. The first composition is introduced into the hydrocolloid, and acts on the inside of the Escherichia coli or the Staphylococcus aureus along with the encapsulation of the Escherichia coli or the Staphylococcus aureus carried by the target of the application of the detergent or bactericide by the hydrocolloid.
用于作用于细菌胞内环境的有机酸的分子直径能够小于大肠杆菌和金黄色葡萄球菌的胞膜通道直径以使有机酸分子能够自胞膜通道进入菌胞内部并破坏菌胞内部的碱性环境从而抑制菌胞活性。The molecular diameter of the organic acid used to act on the bacterial intracellular environment can be smaller than the diameter of the cell membrane channel of Escherichia coli and Staphylococcus aureus so that the organic acid molecule can enter the inside of the cell through the cell membrane channel and destroy the alkalinity inside the cell The environment inhibits bacterial cell activity.
通过苹果酸、甘氨酸和马尿酸构成的第一组合物与柠檬酸或富马酸构成的第二组合物的协同作用,实现大肠杆菌和金黄色葡萄球菌的共同抑制作用。Through the synergistic effect of the first composition composed of malic acid, glycine and hippuric acid and the second composition composed of citric acid or fumaric acid, the co-inhibitory effect of Escherichia coli and Staphylococcus aureus is realized.
实施例5Example 5
本实施例是对实施例1、实施例2、实施例3或实施例4的进一步改进,重复的内容不再赘述。This embodiment is a further improvement on Embodiment 1, Embodiment 2, Embodiment 3 or Embodiment 4, and repeated content will not be repeated.
本发明设计一种组合物,该组合物用于以喷洒、雾化或其他形成小颗粒气体或液体的方式扩散至目标表面并消杀和抑制目标表面的大肠杆菌和金黄色葡萄球菌。The present invention designs a composition, which is used to spread to the target surface by spraying, atomizing or other means of forming small particle gas or liquid, and disinfecting and inhibiting Escherichia coli and Staphylococcus aureus on the target surface.
组合物由组合式液体或气体颗粒构成。上述液体或气体颗粒包含由高效抑菌的有机酸构成的颗粒核心和覆盖颗粒核心的由硅烷偶联剂中和的纳米级无机微孔形态的氧化锆-氧化锡复合体构成的用于保护和增加附着能力的外披膜。Compositions consist of combined liquid or gaseous particles. The above-mentioned liquid or gas particles contain a particle core composed of an efficient antibacterial organic acid and a nano-scale inorganic microporous zirconia-tin oxide composite covering the particle core that is neutralized by a silane coupling agent for protection and protection. Outer mantle for increased adhesion.
通过将包裹有机酸的硅烷偶联剂中和的纳米级无机微孔形态的氧化锆-氧化锡复合体以气雾、气溶胶或小颗粒液体的方式分散于衣物、生活环境中,在包裹有机酸的硅烷偶联剂中和的纳米级无机微孔形态的氧化锆-氧化锡复合体触碰目标表面的大肠杆菌和金黄色葡萄球菌时,外皮膜基于压力释放有机酸并允许有机酸通过细菌表面的胞膜进入细菌体内,从而抑制细菌活性。氧化锆-氧化锡复合体形成的纳米级无机微孔能够允许有机酸分子进出,并限制大体积颗粒对该颗粒的分解和附着的阻碍。氧化锆-氧化锡复合体能够有效的在构成以气溶胶或液体、气体形态存在的颗粒的外披膜时保持外披膜的硬度和防纳米微孔塌陷的韧度。The nano-scale inorganic microporous zirconia-tin oxide composite that is neutralized by the silane coupling agent that wraps the organic acid is dispersed in the clothes and living environment in the form of aerosol, aerosol or small particle liquid. When the zirconia-tin oxide complex in nanoscale inorganic microporous form, which is neutralized by the silane coupling agent of the acid, touches Escherichia coli and Staphylococcus aureus on the target surface, the outer film releases organic acids based on pressure and allows the organic acids to pass through the bacteria The cell membrane on the surface enters the bacterial body, thereby inhibiting bacterial activity. The nanoscale inorganic micropores formed by the zirconia-tin oxide composite can allow organic acid molecules to enter and exit, and limit the hindrance of the decomposition and attachment of large-volume particles to the particles. The zirconia-tin oxide composite can effectively maintain the hardness of the outer coating and the toughness of preventing nano-micropore collapse when forming the outer coating of particles in the form of aerosol, liquid or gas.
优选地,硅烷偶联剂与纳米级无机微孔形态的氧化锆-氧化锡复合体的比例在1:40~1:120。纳米级无机微孔形态氧化锆-氧化锡复合体与有机酸的比例在1:1~1:10之间。Preferably, the ratio of the silane coupling agent to the nanoscale inorganic microporous zirconia-tin oxide composite is 1:40-1:120. The ratio of nanoscale inorganic microporous zirconia-tin oxide composite to organic acid is between 1:1 and 1:10.
由硅烷偶联剂偶联的有机体-无机体构成的微颗粒能够以直径至少小于10μm的状态向目标表面移动。上述微颗粒在用于稀释或均匀液相的水相中具有优良的分散稳定性,携带有机酸在目标表面的高附着率以及由于外皮膜的包裹而降低有机酸核心的高挥发性能。利用低成本的且能够稳定偶联内部的有机层与外部的无机层的中间相,在不损害有机层氢离子的游离的情况下,增加与有机层偶联且不发生其他化学反应的无机层,通过无机层的性质克服了有机层在目标表面附着力差、无作用且易挥发的问题。优选地,硅烷偶联剂偶联能够为水性硅烷偶联剂偶联。Microparticles composed of organic-inorganic bodies coupled with silane coupling agents can move to the target surface with a diameter of at least less than 10 μm. The above-mentioned microparticles have excellent dispersion stability in the water phase for dilute or homogeneous liquid phase, high adhesion rate of carrying organic acid on the target surface, and high volatility performance of reducing the core of organic acid due to the wrapping of the outer film. Using a low-cost mesophase that can stably couple the internal organic layer and the external inorganic layer, increase the inorganic layer that is coupled with the organic layer and does not undergo other chemical reactions without damaging the ionization of hydrogen ions in the organic layer , The properties of the inorganic layer overcome the problems of poor adhesion, no effect and volatile nature of the organic layer on the target surface. Preferably, the coupling with a silane coupling agent can be coupling with an aqueous silane coupling agent.
上述组合物的配制方法如下:The preparation method of above-mentioned composition is as follows:
(1)称量:按照比例称量以重量换算的硅烷偶联剂偶联和氧化锆氧化锡复合体(其能够以溶胶形式存在),称量以体积换算的有机酸组合物;(1) Weighing: Weigh the silane coupling agent coupling and zirconia tin oxide complex (which can exist in the form of sol) in weight conversion according to the proportion, and weigh the organic acid composition in volume conversion;
(2)混合:将氧化锆氧化锡复合体分批次放入有机酸中,混匀,而后伴随搅拌动作缓慢倒入硅烷偶联剂偶联,搅拌至三相均匀,即获得浓缩后的组合物。(2) Mixing: Put the zirconia tin oxide complex into the organic acid in batches, mix well, then slowly pour into the silane coupling agent for coupling with the stirring action, and stir until the three phases are uniform, that is, the concentrated combination is obtained thing.
浓缩后的组合物在使用前能够添加水进行浓度稀释,而后通过气雾机、喷壶等设备向环境或衣物等需要消毒的目标表面喷洒。The concentrated composition can be diluted with water before use, and then sprayed on the target surface requiring disinfection such as the environment or clothing through equipment such as an aerosol machine and a watering can.
上述颗粒核心的有机酸能够与上述实施例中涉及的能够对大肠杆菌和金黄色葡萄球菌的抑菌效果达到MIC为0.1C的有机酸组合物。由本发明中涉及的由外皮膜包裹的有机酸组合在水中具有良好的稳定性,并对大肠杆菌和金黄色葡萄球菌具有高效的抑制效果。The organic acid at the core of the above particles can be combined with the organic acid composition mentioned in the above examples that can have an bacteriostatic effect on Escherichia coli and Staphylococcus aureus with an MIC of 0.1C. The combination of organic acids covered by the outer film involved in the present invention has good stability in water, and has high-efficiency inhibitory effect on Escherichia coli and Staphylococcus aureus.
实施例6Example 6
本实施例是对实施例1、实施例2、实施例3、实施例4或实施例5的进一步改进,重复的内容不再赘述。This embodiment is a further improvement on Embodiment 1, Embodiment 2, Embodiment 3, Embodiment 4 or Embodiment 5, and repeated content will not be repeated.
针对上述能够持久附着于表面并作用于细菌的有机酸组合物,本发明能够设计一种具有苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种的抑菌药膏或喷雾,其能够作用于面部、手臂、重要器官等皮肤表面或黏膜。有机酸组合成分对以大肠杆菌和金色葡萄球菌为代表的革兰氏阴性菌和革兰氏阳性菌等多种致病性皮肤菌的繁衍具有明显的抑菌作用。For the above-mentioned organic acid composition that can be permanently attached to the surface and act on bacteria, the present invention can design a composition containing one of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid. One or more antibacterial ointments or sprays, which can act on the skin surface or mucous membranes such as the face, arms, and vital organs. The organic acid composition has obvious antibacterial effect on the reproduction of various pathogenic skin bacteria such as Escherichia coli and Staphylococcus aureus as representatives of Gram-negative bacteria and Gram-positive bacteria.
优选地,所述抑菌药膏,包括中药膏、中药粉、贻贝粘蛋白和包含苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种的有机酸组合物。Preferably, the antibacterial ointment includes traditional Chinese medicine ointment, traditional Chinese medicine powder, mussel mucin and one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid. Several organic acid compositions.
优选地,所述抑菌喷雾,包含戊二醇、1,3丙二醇和含苹果酸、马尿酸、富马酸、甘氨酸、琥珀酸、L-缬氨酸和柠檬酸中的一种或几种的有机酸组合物。Preferably, the antibacterial spray contains pentylene glycol, 1,3 propylene glycol and one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine and citric acid organic acid composition.
需要注意的是,上述具体实施例是示例性的,本领域技术人员可以在本发明公开内容的启发下想出各种解决方案,而这些解决方案也都属于本发明的公开范围并落入本发明的保护范围之内。本领域技术人员应该明白,本发明说明书及其附图均为说明性而并非构成对权利要求的限制。本发明的保护范围由权利要求及其等同物限定。本发明说明书包含多项发明构思,诸如“优选地”、“根据一个优选实施方式”或“可选地”均表示相应段落公开了一个独立的构思,申请人保留根据每项发明构思提出分案申请的权利。在全文中,“优选地”所引导的特征仅为一种可选方式,不应理解为必须设置,故此申请人保留随时放弃或删除相关优选特征之权利。It should be noted that the above specific embodiments are exemplary, and those skilled in the art can come up with various solutions inspired by the disclosure of the present invention, and these solutions also belong to the scope of the disclosure of the present invention and fall within the scope of this disclosure. within the scope of protection of the invention. Those skilled in the art should understand that the description and drawings of the present invention are illustrative rather than limiting to the claims. The protection scope of the present invention is defined by the claims and their equivalents. The description of the present invention contains a number of inventive concepts, such as "preferably", "according to a preferred embodiment" or "optionally" all indicate that the corresponding paragraph discloses an independent concept, and the applicant reserves the right to propose a division based on each inventive concept right to apply. Throughout the text, the features introduced by "preferably" are only optional, and should not be interpreted as having to be set. Therefore, the applicant reserves the right to waive or delete relevant preferred features at any time.
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