CN116076776A - Electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect - Google Patents

Electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect Download PDF

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CN116076776A
CN116076776A CN202211633208.8A CN202211633208A CN116076776A CN 116076776 A CN116076776 A CN 116076776A CN 202211633208 A CN202211633208 A CN 202211633208A CN 116076776 A CN116076776 A CN 116076776A
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monoamine oxidase
electronic cigarette
atomized liquid
nicotine
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林光榕
吴铁
吴怡
戚怡
叶华
郑周荧
邹丽宜
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Huizhou Happy Vaping Technology Ltd
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Huizhou Happy Vaping Technology Ltd
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Priority to PCT/CN2023/126621 priority patent/WO2024131270A1/en
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    • AHUMAN NECESSITIES
    • A24TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24BMANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10Chemical features of tobacco products or tobacco substitutes
    • A24B15/16Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A24B15/167Chemical features of tobacco products or tobacco substitutes of tobacco substitutes in liquid or vaporisable form, e.g. liquid compositions for electronic cigarettes
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention relates to an electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect, which comprises the following preparation components in parts by weight: 1 to 5 parts of limonene, 1 to 5 parts of linalool, 1 to 5 parts of vanillin, 0.3 to 3 parts of phyllitol, 0.3 to 3 parts of geraniol, 1 to 5 parts of methyl cinnamate, 1 to 5 parts of menthol, 1 to 5 parts of maltol, 1 to 5 parts of benzoic acid, 1 to 5 parts of salvianic acid, 50 to 80 parts of propylene glycol and 10 to 30 parts of glycerin. The electronic cigarette atomized liquid has the beneficial effects that the electronic cigarette atomized liquid has the effect of inhibiting monoamine oxidase, solves the problem that a great amount of absorbed electronic smoke can reach a satisfactory degree due to insufficient activity of the nicotine-containing electronic cigarette atomized liquid on the market at present, solves the problem of addiction finally, gradually achieves the effect of stopping smoking, and simultaneously has the effects of increasing the memory of monoamine oxidase inhibitor, improving thinking, resisting anxiety and resisting depression.

Description

具有抑制单胺氧化酶活性作用的电子烟雾化液E-cigarette liquid with the effect of inhibiting the activity of monoamine oxidase

技术领域technical field

本发明属于电子烟雾化液制备技术领域,特别涉及一种具有抑制单胺氧化酶活性作用的电子烟雾化液。The invention belongs to the technical field of preparation of electronic smog liquid, in particular to an electronic smog liquid capable of inhibiting the activity of monoamine oxidase.

背景技术Background technique

单胺氧化酶(MAO)是人体内天然存在的一种酶,分为单胺氧化酶A(MAO-A)和单胺氧化酶B(MAO-B)。MAO催化氧化单胺类物质发生脱氢反应,产生过氧化氢、氨和醛类物质,而这些产物与细胞的氧化密切相关。单胺氧化酶广泛存在于神经和非神经组织中,神经元胞质内的单胺氧化酶位于线粒体外膜。脑内的单胺氧化酶-A主要在去甲肾上腺素(NE)能及多巴胺(DA)能神经元中表达,单胺氧化酶-B则主要表达在5-羟色胺(5-HT)能神经元、组胺能神经元及胶质细胞中。在体内MAO-A对5-HT和NE有较大的亲和力,MAO-B则主要降解DA和苯乙胺,抑制单胺氧化酶可以增强单胺类递质的信号传递。MAO-A抑制药物系指一类能选择性抑制MAO-A的药物,主要用于治疗抑郁症,其作用机制是其能可逆性且选择性地抑制MAO-A,阻止脑内5-HT和NE降解,同时增加脑内突触间隙5-HT和NE的浓度,起抗抑郁作用。Monoamine oxidase (MAO) is a naturally occurring enzyme in the human body, which is divided into monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). MAO catalyzes the dehydrogenation reaction of oxidized monoamines to produce hydrogen peroxide, ammonia and aldehydes, and these products are closely related to the oxidation of cells. Monoamine oxidase is widely found in nerve and non-nerve tissues, and the monoamine oxidase in the cytoplasm of neurons is located in the outer mitochondrial membrane. Monoamine oxidase-A in the brain is mainly expressed in norepinephrine (NE) and dopamine (DA) neurons, while monoamine oxidase-B is mainly expressed in 5-hydroxytryptamine (5-HT) neurons and histaminergic neurons. Yuan and glial cells. In vivo, MAO-A has a greater affinity for 5-HT and NE, while MAO-B mainly degrades DA and phenethylamine, and inhibiting monoamine oxidase can enhance the signal transmission of monoamine transmitters. MAO-A inhibitory drugs refer to a class of drugs that can selectively inhibit MAO-A, and are mainly used for the treatment of depression. NE degradation, while increasing the concentration of 5-HT and NE in the brain synaptic cleft, play an antidepressant effect.

研究表明,单胺氧化酶活性和神经递质水平之间的关系被证实与神经和精神疾病相关,单胺氧化酶已成为神经药理学中极具价值的治疗靶点。单胺氧化酶-A抑制剂目前被用来治疗焦虑症和抑郁症,自20世纪50年代第一个单胺氧化酶抑制剂依普罗尼嗪被用作抗抑郁药治疗,因为三种主要单胺类物质(如去甲肾上腺素、多巴胺和血清素)的水平在大脑中受到调节。单胺类递质失衡假说是被广泛认可的抑郁症发病机制,在抑郁症患者中,脑内去甲肾上腺素和5-羟色胺水平的降低以及诱导表达MAO-A是抑郁症最重要的致病因素。此外,抑郁症与单胺氧化酶-A功能多态性基因和5-羟色胺基因信号通路有关。在抑郁症情况下,脑内单胺氧化酶A的水平增加。因此传统抗抑郁药物抑制单胺氧化酶A使5-HT信号通路活性降低而发挥治疗效应。单胺氧化酶-A的抑制剂已被发现有抗抑郁的特性,在抑郁症治疗中的应用已有50多年的历史,由于单胺氧化酶-A主要代谢5-HT和NE,因此这种酶的抑制剂主要用于治疗抑郁症。研究表明,单胺氧化酶抑制剂抑制神经递质的脱氨或代谢。单胺氧化酶抑制剂也由其选择性决定:有些抑制剂选择性地抑制MAO-A(如吗氯贝胺),有些选择性地抑制MAO-B(如帕吉林和塞来吉林),有些是非选择性的(如苯乙嗪和曲尼环丙烷),可同时抑制MAO-A和MAO-B。早期的单胺氧化酶抑制剂不可逆地抑制单胺氧化酶,当它们与单胺氧化酶相互作用时,会使酶永久性地失活。之后研发的单胺氧化酶抑制剂,如吗氯贝胺是可逆的,意味着当抑制剂与酶分离时,MAO酶活性可被再次恢复。尽管MAO-A抑制剂是治疗心理疾病的一种治疗机制,但当过量服用MAO-A抑制剂或与其他药物、膳食补充剂或植物药联合使用时,可能会出现一些不良反应,如肝毒性、镇静、认知障碍、运动失调、攻击性、性功能障碍、药物耐受性和依赖性等。同时,肝脏中过度的MAO-A抑制会阻碍饮食中酪胺的代谢,最终导致高血压危机。因此,有必要去寻找替代传统MAO-A抑制剂的天然无毒抑制剂。Studies have shown that the relationship between monoamine oxidase activity and neurotransmitter levels has been confirmed to be relevant to neurological and psychiatric diseases, and monoamine oxidase has become a valuable therapeutic target in neuropharmacology. Monoamine oxidase-A inhibitors are currently used to treat anxiety and depression. levels of norepinephrine, dopamine, and serotonin) are regulated in the brain. The monoamine transmitter imbalance hypothesis is widely recognized as the pathogenesis of depression. In patients with depression, the reduction of norepinephrine and 5-hydroxytryptamine levels in the brain and the induction of MAO-A are the most important pathogenesis of depression. factor. In addition, depression was associated with monoamine oxidase-A functional polymorphism gene and serotonin gene signaling pathway. In the case of depression, levels of monoamine oxidase A in the brain are increased. Therefore, traditional antidepressants inhibit monoamine oxidase A to reduce the activity of 5-HT signaling pathway and play a therapeutic effect. Monoamine oxidase-A inhibitors have been found to have antidepressant properties and have been used in the treatment of depression for more than 50 years. Since monoamine oxidase-A mainly metabolizes 5-HT and NE, inhibitors of this enzyme are mainly used in the treatment of depression. Studies have shown that monoamine oxidase inhibitors inhibit the deamination or metabolism of neurotransmitters. MAO inhibitors are also determined by their selectivity: some inhibitors selectively inhibit MAO-A (eg, moclobemide), some selectively inhibit MAO-B (eg, pagiline and selegiline), and some are nonselective (eg, phenelzine and tranicycline), which inhibit both MAO-A and MAO-B. Early MAO inhibitors inhibited MAO irreversibly, permanently inactivating the enzyme when they interacted with MAO. Later developed monoamine oxidase inhibitors, such as moclobemide, are reversible, meaning that MAO enzyme activity can be restored again when the inhibitor is dissociated from the enzyme. Although MAO-A inhibitors are a therapeutic mechanism in the treatment of psychological disorders, some adverse effects such as hepatotoxicity may occur when MAO-A inhibitors are taken in excess or in combination with other drugs, dietary supplements or botanicals , sedation, cognitive impairment, movement disorders, aggression, sexual dysfunction, drug tolerance and dependence, etc. At the same time, excessive MAO-A inhibition in the liver hinders the metabolism of dietary tyramine, eventually leading to a hypertensive crisis. Therefore, it is necessary to find natural non-toxic inhibitors to replace traditional MAO-A inhibitors.

电子香烟,即电子尼古丁输送系统ENDS,目前由于电子烟不涉及烟草燃烧,尼古丁(烟碱)和其他成分在吸入前被雾化,与传统卷烟相比,不燃烧可以减少电子烟使用者的有毒物质吸收,这类产品逐步被广大吸烟者接受。但由于电子烟中的尼古丁对焦虑等情绪的抑制不如普通香烟,也导致这些含尼古丁的电子烟被大量滥用,从而达不到应用电子烟达到戒烟的目标。研究认为,吸烟者解除精神疲劳,控制焦虑情绪与卷烟烟雾中含有单胺氧化酶(MAO)抑制剂有关,但这种单胺氧化酶抑制剂与尼古丁没有关系,是由β-咔啉类物质导致的,故吸烟后,这种卷烟烟雾可以缓解吸烟者的焦虑情绪,而电子烟雾化液不含有这些物质,就达不到吸烟者想要的效果,因此吸取者为了获得吸烟的有利效果,就要加大吸电子烟雾的用量,就会更容易导致滥用及成瘾。最近有研究表明,烟碱具有抑制MAO-B纯蛋白活性的作用【徐家佳,烟碱抑制单胺氧化酶B活性及其对抗帕金森病作用研究,中国烟草学报,2021,27(3):88】,但对尼古丁是否对单胺氧化酶A也有抑制作用,目前还没有报告。有研究者观察了在大鼠中使用颅内自我刺激(ICSS)比较了含有尼古丁和一系列非尼古丁成分的卷烟烟雾和电子香烟气溶胶提取物与单独的尼古丁(NRT类似物)的相对滥用倾向。观察这些制剂在体外和离体对脑MAO活性的影响,研究者同时还研究了单胺氧化酶抑制在颅内自我刺激研究中的潜在作用。研究者观察到与电子香烟提取物相比,卷烟烟雾提取物含有更高水平的几种具有抑制单胺氧化酶活性的非尼古丁成分(例如,β-carbolines norharmaneand harmane)。单独的尼古丁在中等尼古丁剂量下降低了颅内自我刺激的阈值,表明可能会促进滥用倾向的强化增强效应,而在高尼古丁剂量下升高颅内自我刺激阈值,表明可能会限制滥用倾向的厌恶/快感效应。在高尼古丁剂量下,卷烟烟雾提取物比单独尼古丁更高程度地提高了颅内自我刺激阈值。电子香烟提取物对颅内自我刺激的影响与单独的尼古丁没有区别。研究者观察到,卷烟烟雾提取物在体外显著抑制MAO-A和MAO-B活性,而单独的电子香烟提取物和尼古丁没有。【Andrew C Harris,Cigarette Smoke Extract,but NotElectronic Cigarette Aerosol Extract,Inhibits Monoamine Oxidase in vitro andProduces Greater Acute Aversive/Anhedonic Effects Than Nicotine Alone onIntracranial Self-Stimulation in Rats.Front Neurosci.2022May 25;16:868088.】,这些发现表明,与单独的尼古丁相比,卷烟烟雾提取物具有更大的急性厌恶/快感缺失效应,表明滥用倾向较低。尽管需要使用其他给药方案、临床前成瘾模型和烟草制品提取物来确认这些研究结果,但这些研究结果表明,单胺氧化酶抑制剂和其他非尼古丁成分的中枢介导作用是未来具有抗焦虑功效的电子烟必须添加的成分。Electronic cigarettes, namely electronic nicotine delivery system ENDS, currently because electronic cigarettes do not involve tobacco combustion, nicotine (nicotine) and other components are atomized before inhalation, compared with traditional cigarettes, non-combustion can reduce the toxicity of electronic cigarette users Substance absorption, these products are gradually accepted by the majority of smokers. However, because the nicotine in electronic cigarettes is not as good as ordinary cigarettes in suppressing emotions such as anxiety, these electronic cigarettes containing nicotine are also abused in large quantities, so that the goal of using electronic cigarettes to achieve smoking cessation cannot be achieved. Studies have shown that smokers relieve mental fatigue and control anxiety are related to the monoamine oxidase (MAO) inhibitor contained in cigarette smoke, but this MAO inhibitor has nothing to do with nicotine, it is caused by β-carbolines, so after smoking , this kind of cigarette smoke can relieve the anxiety of the smoker, but the e-cigarette liquid does not contain these substances, and the effect that the smoker wants cannot be achieved. The amount of smoke is more likely to lead to abuse and addiction. Recent studies have shown that nicotine has the effect of inhibiting the activity of MAO-B pure protein [Xu Jiajia, Research on the inhibition of monoamine oxidase B activity by nicotine and its anti-Parkinson's disease effect, China Tobacco Journal, 2021, 27(3): 88], but Whether nicotine also has an inhibitory effect on monoamine oxidase A has not been reported yet. Here we observe the relative abuse of cigarette smoke and e-cigarette aerosol extracts containing nicotine and a range of non-nicotine components to nicotine alone (NRT analogues) using intracranial self-stimulation (ICSS) in rats. tendency. Looking at the effects of these agents on brain MAO activity in vitro and ex vivo, the researchers also investigated the potential role of monoamine oxidase inhibition in intracranial self-stimulation studies. The researchers observed that cigarette smoke extracts contained higher levels of several non-nicotine components (eg, β-carbolines norharmane and harmane) with monoamine oxidase-inhibiting activity compared with e-cigarette extracts. Nicotine alone lowers the threshold of intracranial self-stimulation at moderate nicotine doses, suggesting a reinforcing potentiating effect that may promote abuse propensity, whereas it increases threshold of intracranial self-stimulation at high nicotine doses, suggesting aversion that may limit abuse propensity / Pleasure effect. At high nicotine doses, cigarette smoke extracts increased intracranial self-stimulation thresholds to a greater extent than nicotine alone. E-cigarette extracts had no different effects on intracranial self-stimulation than nicotine alone. The researchers observed that cigarette smoke extract significantly inhibited MAO-A and MAO-B activity in vitro, while e-cigarette extract and nicotine alone did not. [Andrew C Harris, Cigarette Smoke Extract, but NotElectronic Cigarette Aerosol Extract, Inhibits Monoamine Oxidase in vitro and Produces Greater Acute Aversive/Anhedonic Effects Than Nicotine Alone on Intracranial Self-Stimulation in Rats.Front Neurosci.2022May 25;16:868088.], these The findings indicated that cigarette smoke extract had a greater acute aversive/anhedonic effect than nicotine alone, indicating a lower propensity for abuse. Although confirmation of these findings using other dosing regimens, preclinical addiction models, and tobacco product extracts is required, these findings suggest that centrally mediated effects of MAOIs and other non-nicotine ingredients are future candidates for anxiolytic efficacy Ingredients that must be added to e-cigarettes.

发明内容Contents of the invention

本发明的目的是提供一种具有抑制单胺氧化酶活性作用的电子烟雾化液,经过大量的实验药物组合及实验观察,我们找到了一种特别具有抑制单胺氧化酶A活性的电子烟雾化液,该雾化液可以保持电子烟尼古丁的特性及风味,还具有抗焦虑抗抑郁的单胺氧化酶A抑制剂的作用。The purpose of the present invention is to provide an electronic smog liquid that can inhibit the activity of monoamine oxidase A. After a large number of experimental drug combinations and experimental observations, we have found an electronic smog liquid that can especially inhibit the activity of monoamine oxidase A. The atomized liquid It can maintain the characteristics and flavor of nicotine in electronic cigarettes, and also has the effect of anti-anxiety and anti-depressant monoamine oxidase A inhibitor.

本发明的技术解决方案是,一种具有抑制单胺氧化酶活性作用的电子烟雾化液,其配制组分按重量份包括:柠檬烯1~5份,芳樟醇1~5份,香兰素1~5份,叶醇0.3~3份,香叶醇0.3~3份,肉桂酸甲酯1~5份,薄荷醇1~5份,麦芽酚1~5份,苯甲酸1~5份,丹参素1~5份,丙二醇50~80份,甘油10~30份。The technical solution of the present invention is an electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase. 0.3-3 parts of leaf alcohol, 0.3-3 parts of geraniol, 1-5 parts of methyl cinnamate, 1-5 parts of menthol, 1-5 parts of maltol, 1-5 parts of benzoic acid, 1 part of Danshensu ~5 parts, 50~80 parts of propylene glycol, 10~30 parts of glycerin.

优选地,其配制组分按重量份还包括:烟碱0.1~5份。Preferably, the preparation components further include: 0.1-5 parts of nicotine in parts by weight.

优选地,其配制组分按重量份还包括:柚皮苷1~5份。Preferably, its preparation components also include: 1-5 parts of naringin in parts by weight.

优选地,其配制组分按重量份还包括:烟碱0.1~5份,柚皮苷1~5份。Preferably, the preparation components further include: 0.1-5 parts of nicotine and 1-5 parts of naringin in parts by weight.

优选地,所述柠檬烯2~4份,所述芳樟醇1.2~3份,所述香兰素1.5~3份,所述叶醇0.5~2份,所述香叶醇0.5~1.5份,所述肉桂酸甲酯1.2~2份,所述薄荷醇1~3份,所述麦芽酚1~2份,所述苯甲酸1~2份,所述丹参素1~2份,所述丙二醇71~78份,所述甘油11~15份。Preferably, 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of leaf alcohol, 0.5-1.5 parts of geraniol, 1.2 to 2 parts of methyl cinnamate, 1 to 3 parts of menthol, 1 to 2 parts of maltol, 1 to 2 parts of benzoic acid, 1 to 2 parts of danshensu, and 1 to 2 parts of propylene glycol 71 to 78 parts, and 11 to 15 parts of glycerol.

优选地,所述柠檬烯2.5份,所述芳樟醇1.5份,所述香兰素2份,所述叶醇0.5份,所述香叶醇0.5份,所述肉桂酸甲酯1.5份,所述薄荷醇1.5份,所述麦芽酚1份,所述苯甲酸1份,所述丹参素1份,所述丙二醇74.5份,所述甘油12.5份。Preferably, 2.5 parts of the limonene, 1.5 parts of the linalool, 2 parts of the vanillin, 0.5 parts of the leaf alcohol, 0.5 parts of the geraniol, 1.5 parts of the methyl cinnamate, the 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of danshensu, 74.5 parts of propylene glycol, and 12.5 parts of glycerin.

优选地,所述柠檬烯2~4份,所述芳樟醇1.2~3份,所述香兰素1.5~3份,所述叶醇0.5~2份,所述香叶醇0.5~1.5份,所述肉桂酸甲酯1.2~2份,所述薄荷醇1~3份,所述麦芽酚1~2份,所述苯甲酸1~2份,所述丹参素1~2份,所述丙二醇71~78份,所述甘油11~15份,所述烟碱0.2~2份。Preferably, 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of leaf alcohol, 0.5-1.5 parts of geraniol, 1.2 to 2 parts of methyl cinnamate, 1 to 3 parts of menthol, 1 to 2 parts of maltol, 1 to 2 parts of benzoic acid, 1 to 2 parts of danshensu, and 1 to 2 parts of propylene glycol 71-78 parts, 11-15 parts of glycerin, and 0.2-2 parts of nicotine.

优选地,所述柠檬烯2.5份,所述芳樟醇1.5份,所述香兰素2份,所述叶醇0.5份,所述香叶醇0.5份,所述肉桂酸甲酯1.5份,所述薄荷醇1.5份,所述麦芽酚1份,所述苯甲酸1份,所述丹参素1份,所述丙二醇74份,所述甘油12.5份,所述烟碱0.5份。Preferably, 2.5 parts of the limonene, 1.5 parts of the linalool, 2 parts of the vanillin, 0.5 parts of the leaf alcohol, 0.5 parts of the geraniol, 1.5 parts of the methyl cinnamate, the 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of danshensu, 74 parts of propylene glycol, 12.5 parts of glycerin, and 0.5 part of nicotine.

优选地,所述柠檬烯2~4份,所述芳樟醇1.2~3份,所述香兰素1.5~3份,所述叶醇0.5~2份,所述香叶醇0.5~1.5份,所述肉桂酸甲酯1.2~2份,所述薄荷醇1~3份,所述麦芽酚1~2份,所述苯甲酸1~2份,所述丹参素1~2份,所述丙二醇71~78份,所述甘油11~15份,所述柚皮苷1~3份。Preferably, 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of leaf alcohol, 0.5-1.5 parts of geraniol, 1.2 to 2 parts of methyl cinnamate, 1 to 3 parts of menthol, 1 to 2 parts of maltol, 1 to 2 parts of benzoic acid, 1 to 2 parts of danshensu, and 1 to 2 parts of propylene glycol 71-78 parts, 11-15 parts of glycerin, and 1-3 parts of naringin.

优选地,所述柠檬烯2.5份,所述芳樟醇1.5份,所述香兰素2份,所述叶醇0.5份,所述香叶醇0.5份,所述肉桂酸甲酯1.5份,所述薄荷醇1.5份,所述麦芽酚1份,所述苯甲酸1份,所述丹参素1份,所述丙二醇74份,所述甘油12份,所述柚皮苷1份。Preferably, 2.5 parts of the limonene, 1.5 parts of the linalool, 2 parts of the vanillin, 0.5 parts of the leaf alcohol, 0.5 parts of the geraniol, 1.5 parts of the methyl cinnamate, the 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of danshensu, 74 parts of propylene glycol, 12 parts of glycerin, and 1 part of naringin.

优选地,所述柠檬烯2~4份,所述芳樟醇1.2~3份,所述香兰素1.5~3份,所述叶醇0.5~2份,所述香叶醇0.5~1.5份,所述肉桂酸甲酯1.2~2份,所述薄荷醇1~3份,所述麦芽酚1~2份,所述苯甲酸1~2份,所述丹参素1~2份,所述丙二醇71~78份,所述甘油11~15份,所述烟碱0.2~2份,所述柚皮苷1~3份。Preferably, 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of leaf alcohol, 0.5-1.5 parts of geraniol, 1.2 to 2 parts of methyl cinnamate, 1 to 3 parts of menthol, 1 to 2 parts of maltol, 1 to 2 parts of benzoic acid, 1 to 2 parts of danshensu, and 1 to 2 parts of propylene glycol 71-78 parts, 11-15 parts of glycerin, 0.2-2 parts of nicotine, and 1-3 parts of naringin.

优选地,所述柠檬烯2.5份,所述芳樟醇1.5份,所述香兰素2份,所述叶醇0.5份,所述香叶醇0.5份,所述肉桂酸甲酯1.5份,所述薄荷醇1.5份,所述麦芽酚1份,所述苯甲酸1份,所述丹参素1份,所述丙二醇73.5份,所述甘油12份,所述烟碱0.5份,所述柚皮苷1份。Preferably, 2.5 parts of the limonene, 1.5 parts of the linalool, 2 parts of the vanillin, 0.5 parts of the leaf alcohol, 0.5 parts of the geraniol, 1.5 parts of the methyl cinnamate, the 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of danshensu, 73.5 parts of propylene glycol, 12 parts of glycerin, 0.5 part of nicotine, and 1 part of pomelo peel glycosides 1 part.

综上,与现有技术相比,本发明的有益效果是:本发明以丹参素和香兰素为添加剂制备的以抑制单胺氧化酶活性为主要功效的电子烟雾化液,解决了以目前市面上的含尼古丁的电子烟雾化液抑制单胺氧化酶活性不足而存在的要大量吸收电子烟雾才能达到满意的程度,解决了最终导致成瘾性问题,最终达到戒烟的作用。本发明提供的不含尼古丁的电子烟雾化液和含尼古丁的电子烟雾化液,都因为具有明显抑制单胺氧化酶的作用而达到了吸烟者想获得的吸烟后可以减轻紧张焦虑等心理压力或精神状态,从而减轻继续吸烟的愿望,逐步达到戒烟的目标。另外,本发明在电子烟雾化液的溶剂中,还添加柠檬烯和芳樟醇,可以改善电子烟雾化液的口感和风味,特别是没有喉咙干燥的感觉、没有残留物积聚和增加风味强度,同时,也具有单胺氧化酶抑制剂的增加记忆,改善思维,抗焦虑,抗抑郁的作用。To sum up, compared with the prior art, the beneficial effects of the present invention are: the present invention uses danshensu and vanillin as additives to prepare the electronic smog liquid with the main effect of inhibiting the activity of monoamine oxidase, which solves the problem of containing The nicotine e-cigarette liquid inhibits the activity of monoamine oxidase due to the lack of activity and needs to absorb a large amount of e-cigarettes to achieve a satisfactory level, which solves the problem of addiction and finally achieves the effect of smoking cessation. Both the nicotine-free electronic cigarette liquid and the nicotine-containing electronic cigarette liquid provided by the present invention have the effect of significantly inhibiting monoamine oxidase, so that they can reduce the psychological stress or mental state such as tension and anxiety that smokers want after smoking. Thereby reducing the desire to continue smoking, and gradually achieve the goal of smoking cessation. In addition, the present invention also adds limonene and linalool to the solvent of the e-cigarette liquid, which can improve the taste and flavor of the e-cig liquid, especially without the feeling of dry throat, no residue accumulation, and increased flavor intensity. , also has the effects of increasing memory, improving thinking, anti-anxiety, and anti-depressant effects of monoamine oxidase inhibitors.

具体实施方式Detailed ways

本发明下面将结合实施例作进一步详述:The present invention will be described in further detail below in conjunction with embodiment:

本发明阐述的是一种具有抑制单胺氧化酶活性作用的电子烟雾化液,即在配制电子烟雾化液的过程中,将具有抑制单胺氧化酶功效的组分如柠檬烯、芳樟醇、香兰素、叶醇、香叶醇、肉桂酸甲酯、薄荷醇、麦芽酚、苯甲酸、丹参素、柚皮苷等按重量配比加入其中。The present invention describes an e-cigarette liquid that can inhibit the activity of monoamine oxidase, that is, in the process of preparing the e-cigarette liquid, components that have the effect of inhibiting monoamine oxidase, such as limonene, linalool, vanillin, leaf alcohol , geraniol, methyl cinnamate, menthol, maltol, benzoic acid, danshensu, naringin, etc. are added in proportion by weight.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯1~5份,芳樟醇1~5份,香兰素1~5份,叶醇0.3~3份,香叶醇0.3~3份,肉桂酸甲酯1~5份,薄荷醇1~5份,麦芽酚1~5份,苯甲酸1~5份,丹参素1~5份,丙二醇50~80份,甘油10~30份。One embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the atomized liquid include by weight: 1-5 parts of limonene, 1-5 parts of linalool, 1-5 parts of vanillin 5 parts, 0.3-3 parts of leaf alcohol, 0.3-3 parts of geraniol, 1-5 parts of methyl cinnamate, 1-5 parts of menthol, 1-5 parts of maltol, 1-5 parts of benzoic acid, Danshensu 1-5 parts, 50-80 parts of propylene glycol, 10-30 parts of glycerin.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的另一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯1~5份,芳樟醇1~5份,香兰素1~5份,叶醇0.3~3份,香叶醇0.3~3份,肉桂酸甲酯1~5份,薄荷醇1~5份,麦芽酚1~5份,苯甲酸1~5份,丹参素1~5份,丙二醇50~80份,甘油10~30份,烟碱0.1~5份。Another embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the liquid include by weight: 1-5 parts of limonene, 1-5 parts of linalool, 1 part of vanillin ~5 parts, 0.3~3 parts of leaf alcohol, 0.3~3 parts of geraniol, 1~5 parts of methyl cinnamate, 1~5 parts of menthol, 1~5 parts of maltol, 1~5 parts of benzoic acid, Salvia miltiorrhiza 1 to 5 parts of vegetarian food, 50 to 80 parts of propylene glycol, 10 to 30 parts of glycerin, and 0.1 to 5 parts of nicotine.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的又一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯1~5份,芳樟醇1~5份,香兰素1~5份,叶醇0.3~3份,香叶醇0.3~3份,肉桂酸甲酯1~5份,薄荷醇1~5份,麦芽酚1~5份,苯甲酸1~5份,丹参素1~5份,丙二醇50~80份,甘油10~30份,柚皮苷1~5份。Another embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the liquid include by weight: 1-5 parts of limonene, 1-5 parts of linalool, 1 part of vanillin ~5 parts, 0.3~3 parts of leaf alcohol, 0.3~3 parts of geraniol, 1~5 parts of methyl cinnamate, 1~5 parts of menthol, 1~5 parts of maltol, 1~5 parts of benzoic acid, Salvia miltiorrhiza 1 to 5 parts of vegetable oil, 50 to 80 parts of propylene glycol, 10 to 30 parts of glycerin, and 1 to 5 parts of naringin.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的又一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯1~5份,芳樟醇1~5份,香兰素1~5份,叶醇0.3~3份,香叶醇0.3~3份,肉桂酸甲酯1~5份,薄荷醇1~5份,麦芽酚1~5份,苯甲酸1~5份,丹参素1~5份,丙二醇50~80份,甘油10~30份,烟碱0.1~5份,柚皮苷1~5份。Another embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the liquid include by weight: 1-5 parts of limonene, 1-5 parts of linalool, 1 part of vanillin ~5 parts, 0.3~3 parts of leaf alcohol, 0.3~3 parts of geraniol, 1~5 parts of methyl cinnamate, 1~5 parts of menthol, 1~5 parts of maltol, 1~5 parts of benzoic acid, Salvia miltiorrhiza 1 to 5 parts of vegetable oil, 50 to 80 parts of propylene glycol, 10 to 30 parts of glycerin, 0.1 to 5 parts of nicotine, and 1 to 5 parts of naringin.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的又一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯2~4份,芳樟醇1.2~3份,香兰素1.5~3份,叶醇0.5~2份,香叶醇0.5~1.5份,肉桂酸甲酯1.2~2份,薄荷醇1~3份,麦芽酚1~2份,苯甲酸1~2份,丹参素1~2份,丙二醇71~78份,甘油11~15份。Another embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the liquid include by weight: 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5 parts of vanillin ~3 parts, 0.5~2 parts of leaf alcohol, 0.5~1.5 parts of geraniol, 1.2~2 parts of methyl cinnamate, 1~3 parts of menthol, 1~2 parts of maltol, 1~2 parts of benzoic acid, Salvia miltiorrhiza 1-2 parts of vegetable, 71-78 parts of propylene glycol, 11-15 parts of glycerin.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的又一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯2~4份,芳樟醇1.2~3份,香兰素1.5~3份,叶醇0.5~2份,香叶醇0.5~1.5份,肉桂酸甲酯1.2~2份,薄荷醇1~3份,麦芽酚1~2份,苯甲酸1~2份,丹参素1~2份,丙二醇71~78份,甘油11~15份,烟碱0.2~2份。Another embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the liquid include by weight: 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5 parts of vanillin ~3 parts, 0.5~2 parts of leaf alcohol, 0.5~1.5 parts of geraniol, 1.2~2 parts of methyl cinnamate, 1~3 parts of menthol, 1~2 parts of maltol, 1~2 parts of benzoic acid, Salvia miltiorrhiza 1 to 2 parts of vegetarian food, 71 to 78 parts of propylene glycol, 11 to 15 parts of glycerin, and 0.2 to 2 parts of nicotine.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的又一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯2~4份,芳樟醇1.2~3份,香兰素1.5~3份,叶醇0.5~2份,香叶醇0.5~1.5份,肉桂酸甲酯1.2~2份,薄荷醇1~3份,麦芽酚1~2份,苯甲酸1~2份,丹参素1~2份,丙二醇71~78份,甘油11~15份,柚皮苷1~3份。Another embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the liquid include by weight: 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5 parts of vanillin ~3 parts, 0.5~2 parts of leaf alcohol, 0.5~1.5 parts of geraniol, 1.2~2 parts of methyl cinnamate, 1~3 parts of menthol, 1~2 parts of maltol, 1~2 parts of benzoic acid, Salvia miltiorrhiza 1 to 2 parts of vegetable oil, 71 to 78 parts of propylene glycol, 11 to 15 parts of glycerin, and 1 to 3 parts of naringin.

本发明具有抑制单胺氧化酶活性作用的电子烟雾化液的又一个实施方案是,配制该雾化液的组分按重量份包括:柠檬烯2~4份,芳樟醇1.2~3份,香兰素1.5~3份,叶醇0.5~2份,香叶醇0.5~1.5份,肉桂酸甲酯1.2~2份,薄荷醇1~3份,麦芽酚1~2份,苯甲酸1~2份,丹参素1~2份,丙二醇71~78份,甘油11~15份,烟碱0.2~2份,柚皮苷1~3份。Another embodiment of the electronic smog liquid with the effect of inhibiting the activity of monoamine oxidase of the present invention is that the components for preparing the liquid include by weight: 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5 parts of vanillin ~3 parts, 0.5~2 parts of leaf alcohol, 0.5~1.5 parts of geraniol, 1.2~2 parts of methyl cinnamate, 1~3 parts of menthol, 1~2 parts of maltol, 1~2 parts of benzoic acid, Salvia miltiorrhiza 1 to 2 parts of vegetable oil, 71 to 78 parts of propylene glycol, 11 to 15 parts of glycerin, 0.2 to 2 parts of nicotine, and 1 to 3 parts of naringin.

本发明具体的实施例如下:Concrete embodiments of the present invention are as follows:

实施例一Embodiment one

不含尼古丁的具有抑制单胺氧化酶A活性作用的电子烟雾化液,这里称之为解郁1号电子烟雾化液,配制时按重量份称取以下各组分:柠檬烯2.5份,芳樟醇1.5份,香兰素2份,叶醇0.5份,香叶醇0.5份,肉桂酸甲酯1.5份,薄荷醇1.5份,麦芽酚1份,苯甲酸1份,丹参素1份,丙二醇74.5份,甘油12.5份,然后将上述各组分进行混合、适当加温充分溶解即得。The nicotine-free e-cigarette liquid that has the effect of inhibiting the activity of monoamine oxidase A is called Jieyu No. 1 e-cigarette liquid, and the following components are weighed in parts by weight during preparation: 2.5 parts of limonene, 1.5 parts of linalool , 2 parts of vanillin, 0.5 parts of leaf alcohol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of danshensu, 74.5 parts of propylene glycol, glycerin 12.5 parts, then mix the above-mentioned components, heat properly and dissolve fully.

实施例二Embodiment two

含尼古丁的具有抑制单胺氧化酶A活性作用的电子烟雾化液,这里称之为解郁2号电子烟雾化液,配制时按重量份称取以下各组分:柠檬烯2.5份,芳樟醇1.5份,香兰素2份,叶醇0.5份,香叶醇0.5份,肉桂酸甲酯1.5份,薄荷醇1.5份,麦芽酚1份,苯甲酸1份,丹参素1份,丙二醇74份,甘油12.5份,烟碱0.5份,然后将上述各组分进行混合、适当加温充分溶解即得。The nicotine-containing e-cigarette liquid that can inhibit the activity of monoamine oxidase A is called Jieyu No. 2 e-cig liquid, and the following components are weighed in parts by weight during preparation: 2.5 parts of limonene, 1.5 parts of linalool, 2 parts of vanillin, 0.5 parts of leaf alcohol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of danshensu, 74 parts of propylene glycol, 12.5 parts of glycerin part, 0.5 part of nicotine, and then the above-mentioned components are mixed, properly heated and fully dissolved.

实施例三Embodiment Three

不含尼古丁的具有抑制单胺氧化酶A活性作用的电子烟雾化液,这里称之为解郁3号电子烟雾化液,配制时按重量份称取以下各组分:柠檬烯2.5份,芳樟醇1.5份,香兰素2份,叶醇0.5份,香叶醇0.5份,肉桂酸甲酯1.5份,薄荷醇1.5份,麦芽酚1份,苯甲酸1份,丹参素1份,丙二醇74份,甘油12份,柚皮苷1份,然后将上述各组分进行混合、适当加温充分溶解即得。The nicotine-free e-cigarette liquid that can inhibit the activity of monoamine oxidase A is called Jieyu No. 3 e-cigarette liquid, and the following components are weighed in parts by weight during preparation: 2.5 parts of limonene, 1.5 parts of linalool , 2 parts of vanillin, 0.5 parts of leaf alcohol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of danshensu, 74 parts of propylene glycol, glycerin 12 parts, 1 part of naringin, and then mix the above-mentioned components, heat properly and dissolve fully.

实施例四Embodiment four

含尼古丁的具有抑制单胺氧化酶A活性作用的电子烟雾化液,这里称之为解郁4号电子烟雾化液,配制时按重量份称取以下各组分:其配制组分按重量份包括:柠檬烯2.5份,芳樟醇1.5份,香兰素2份,叶醇0.5份,香叶醇0.5份,肉桂酸甲酯1.5份,薄荷醇1.5份,麦芽酚1份,苯甲酸1份,丹参素1份,丙二醇73.5份,甘油12份,烟碱0.5份,柚皮苷1份,然后将上述各组分进行混合、适当加温充分溶解即得。The nicotine-containing e-cigarette liquid that can inhibit the activity of monoamine oxidase A is called Jieyu No. 4 e-cig liquid, and the following components are weighed in parts by weight during preparation: the preparation components include: limonene in parts by weight 2.5 parts, 1.5 parts of linalool, 2 parts of vanillin, 0.5 parts of leaf alcohol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, Danshensu 1 part, 73.5 parts of propylene glycol, 12 parts of glycerin, 0.5 part of nicotine, 1 part of naringin, and then mix the above-mentioned components, heat properly and fully dissolve.

实验论证Experimental proof

本发明以上实施方案和实施例中,我们通过体外单胺氧化酶的检测方法做了大量的实验,其中,我们选择了abnova公司的试剂盒,该说明书指出单胺氧化酶是一个线粒体酶家族,可催化单胺的氧化脱氨作用。MAO存在两种亚型,MAO-A和MAO-B,具有不同的抑制剂选择性和组织分布。MAO功能障碍被认为是导致许多神经系统疾病的原因。体内异常高或低水平的MAOs与抑郁、精神分裂症、药物滥用、注意力缺陷障碍、偏头痛和性成熟不规律有关。MAO抑制剂是治疗抑郁症、帕金森氏症和阿尔茨海默氏病的主要药物之一。该MAO抑制剂筛选检测试剂盒为筛选MAO酶抑制剂提供了一种方便的荧光测定手段。在实验中,MAO与p-酪胺,即MAO-A和MAO-B的底物发生反应,形成H2O2,采用荧光法(em/ex=585/530nm)测定。该检测方法简单、灵敏、稳定、高通量适应性强。In the above embodiments and examples of the present invention, we have done a lot of experiments through the detection method of monoamine oxidase in vitro, among which, we have chosen the kit of abnova company, the instructions point out that monoamine oxidase is a mitochondrial enzyme family, which can catalyze the oxidation of monoamine Deamination. There are two isoforms of MAO, MAO-A and MAO-B, with different inhibitor selectivity and tissue distribution. MAO dysfunction is thought to be the cause of many neurological diseases. Abnormally high or low levels of MAOs in the body have been linked to depression, schizophrenia, substance abuse, attention deficit disorder, migraines, and irregular sexual maturation. MAO inhibitors are one of the main drugs in the treatment of depression, Parkinson's disease and Alzheimer's disease. The MAO inhibitor screening and detection kit provides a convenient fluorescence measurement means for screening MAO enzyme inhibitors. In the experiment, MAO reacted with p-tyramine, the substrate of MAO-A and MAO-B, to form H2O2, which was measured by fluorescence method (em/ex=585/530nm). The detection method is simple, sensitive, stable, and highly adaptable to high throughput.

实验目的:观察实施例一到实施例四提出的研究解郁1号,解郁2号,解郁3号和解郁4号,是否能抑制MAO-A的活性。Purpose of the experiment: To observe whether Jieyu No. 1, Jieyu No. 2, Jieyu No. 3 and Jieyu No. 4 proposed in Examples 1 to 4 can inhibit the activity of MAO-A.

实验器材:精密电子天平、称量纸、称量匙、0.2-2ul移液枪、0.5-10ul移液枪、10-100ul移液枪、20-200ul移液枪、100-1000ul移液枪、1.5mlEP管、10mlEP管、水浴锅、黑色96孔板、恒温箱、计时器、多功能微孔板检测系统、Monoamine Oxidase Inhibitor ScreeningAssay Kit、MAO-A。Experimental equipment: precision electronic balance, weighing paper, weighing spoon, 0.2-2ul pipette gun, 0.5-10ul pipette gun, 10-100ul pipette gun, 20-200ul pipette gun, 100-1000ul pipette gun, 1.5ml EP tube, 10ml EP tube, water bath, black 96-well plate, incubator, timer, multifunctional microplate detection system, Monoamine Oxidase Inhibitor Screening Assay Kit, MAO-A.

实验原理:用荧光法(EM/EX=585/530nm)测定MAO与MAO-A和MAO-B的底物对酪胺反应生成H2O2。利用计算公式:MAO Activity%=[(RFUTest Cpd-RFUBlank)/(RFUNoInhibitor-RFUBlank)]*100%,算出MAO与MAO-A和MAO-B的活性。该方法简便、灵敏、稳定、适应性强。Experimental principle: use the fluorescence method (EM/EX=585/530nm) to measure the reaction of MAO with the substrates of MAO-A and MAO-B to tyramine to generate H2O2. Using the calculation formula: MAO Activity%=[(RFUTest Cpd-RFUBlank)/(RFUNoInhibitor-RFUBlank)]*100%, calculate the activities of MAO, MAO-A and MAO-B. The method is simple, sensitive, stable and adaptable.

实验方法experimental method

1.实验研究药物的配制1. Preparation of Drugs for Experimental Study

实验药物及配方见表1:Experimental drugs and formulations are shown in Table 1:

表1:具有抑制单胺氧化酶活性作用的电子烟雾化液配方Table 1: E-cigarette liquid formulations with the effect of inhibiting the activity of monoamine oxidase

Figure BDA0004006272050000081
Figure BDA0004006272050000081

2.MAO-A的稀释:取345U/ml的MAO-A 4ul加入DH2O 456ul,稀释纯化MAO-A至3U/ml;2. Dilution of MAO-A: Take 4ul of 345U/ml MAO-A and add DH2O 456ul to dilute and purify MAO-A to 3U/ml;

3.根据Monoamine Oxidase Inhibitor Screening Assay Kit说明书进行操作:3. Operate according to the instructions of Monoamine Oxidase Inhibitor Screening Assay Kit:

(1)阳性对照药物(单胺氧化酶A抑制剂氯吉灵clorgyline)的稀释:取20mMclorgyline 1ul加入DH2O 2ml稀释成10uM clorgyline;(1) Dilution of positive control drug (monoamine oxidase A inhibitor clorgyline): take 20mMclorgyline 1ul and add DH2O 2ml to dilute to 10uM clorgyline;

(2)实验设置空白组、对照组、抑制剂组、解郁1号、解郁2号、解郁3号和解郁4号,实验平行两次;(2) The experiment set up a blank group, a control group, an inhibitor group, Jieyu No. 1, Jieyu No. 2, Jieyu No. 3 and Jieyu No. 4, and the experiment was performed twice in parallel;

(3)在黑色96孔板中依次加入:(3) Add in sequence to the black 96-well plate:

空白组:Blank group: 45ulMAO-A45ul MAO-A 5ul丙二醇:甘油=6:15ul propylene glycol: glycerol = 6:1 对照组:Control group: 45ulMAO-A45ul MAO-A 5ul丙二醇:甘油=6:15ul propylene glycol: glycerol = 6:1 抑制剂:Inhibitors: 45ulMAO-A45ul MAO-A 5ul 10uM clorgyline5ul 10uM clorgyline 药物1:Drug 1: 45ulMAO-A45ul MAO-A 5ul解郁1号5ul Jieyu No.1 药物2:Drug 2: 45ulMAO-A45ul MAO-A 5ul解郁2号5ul Jieyu No. 2 药物3:Drug 3: 45ulMAO-A45ul MAO-A 5ul解郁3号5ul Jieyu No.3 药物4:Drug 4: 45ulMAO-A45ul MAO-A 5ul解郁4号5ul Jieyu No.4

(4)将黑色96孔板放入25℃恒温箱15min;(4) Put the black 96-well plate in a 25°C incubator for 15 minutes;

(5)底物(P-Tyramme)的配制:取P-Tyramme 8ul加入DH2O 4ul配制成1.5倍P-Tyramme;(5) Preparation of substrate (P-Tyramme): Take 8ul of P-Tyramme and add DH2O 4ul to make 1.5 times P-Tyramme;

(6)空白工作液与工作液的配制:(6) Preparation of blank working solution and working solution:

Figure BDA0004006272050000091
Figure BDA0004006272050000091

(7)空白组加入50ul空白工作液,其余组加入50ul工作液,黑暗条件下反应20min,在EM/EX=585/530nm处读取荧光强度。(7) Add 50ul blank working solution to the blank group, add 50ul working solution to the other groups, react for 20min under dark conditions, and read the fluorescence intensity at EM/EX=585/530nm.

(8)根据公式,算出药物1组,药物2组、药物3组和药物4组的MAO-A的活性。(8) According to the formula, calculate the activity of MAO-A of drug 1 group, drug 2 group, drug 3 group and drug 4 group.

4.实验数据记录:4. Experimental data recording:

实验结果见表2:The experimental results are shown in Table 2:

表2:各组实验药物的实验结果Table 2: Experimental results of experimental drugs in each group

实验结果:Experimental results: 空白组blank group 对照组control group 抑制剂Inhibitor 药物1drug 1 药物2drug 2 1孔1 hole 1889018890 472398472398 1633416334 213902213902 111375111375 2孔2 holes 1801418014 491319491319 1522615226 219780219780 120950120950 均值average 1845218452 481858.5481858.5 1578015780 216841216841 116162.5116162.5

5.各组实验药物对单胺氧化酶的抑制活性:5. The inhibitory activity of each group of experimental drugs on monoamine oxidase:

各实验药物对单胺氧化酶的活性作用见表3:The active effects of each experimental drug on monoamine oxidase are shown in Table 3:

表3:各实验药物对单胺氧化酶的活性作用Table 3: The effect of each experimental drug on the activity of monoamine oxidase

检测数据Test data 标准数据standard data 酶活性Enzyme activity 抑酶率Inhibition rate 对照组control group 481858.5481858.5 463406.5463406.5 100.00%100.00% 00 抑制剂Inhibitor 1578015780 -2672-2672 -0.58%-0.58% 100.58%100.58% 解郁1号Jieyu No.1 216841216841 198389198389 42.81%42.81% 57.19%57.19% 解郁2号Jie Yu No. 2 116162.5116162.5 97710.597710.5 21.09%21.09% 78.91%78.91% 解郁3号Jieyu No.3 238683.5238683.5 220231.5220231.5 47.52%47.52% 52.48%52.48% 解郁4号Jieyu No.4 9568095680 7722877228 16.67%16.67% 83.33%83.33%

6.实验结论:6. Experimental conclusion:

本实验应用了单胺氧化酶A进行了活性观察,本实验对照组的活性为100%,阳性对照药单胺氧化酶A抑制剂氯吉灵(clorgyline)抑酶的活性为-0.58%,即其抑酶率也达到100.58%;解郁1号的MAO-A活性为42.81%,其抑酶率为57.19%,解郁2号的MAO-A活性为21.09%;其抑酶率为78.91%,解郁3号的MAO-A活性为47.52%;其抑酶率为52.48%,解郁4号的MAO-A活性为16.67%;其抑酶率为83.33%。研究结果表明,这四种观察药物均有抑制单胺氧化酶A的活性作用,解郁4号和解郁2号抑制单胺氧化酶A的活性更好,这两种制剂的配方均含有尼古丁。提示了含有尼古丁的组方对单胺氧化酶-A活性抑制能力更强。In this experiment, monoamine oxidase A was used to observe the activity. The activity of the control group in this experiment was 100%, and the activity of positive control drug monoamine oxidase A inhibitor clorgyline was -0.58%, that is, the enzyme inhibition rate also reached 100.58%; the MAO-A activity of Jieyu No. 1 was 42.81%, and its enzyme inhibition rate was 57.19%. The MAO-A activity of Jieyu No. 2 was 21.09%; MAO-A activity was 47.52%; its enzyme inhibition rate was 52.48%, MAO-A activity of Jieyu 4 was 16.67%; its enzyme inhibition rate was 83.33%. The results of the study showed that the four observed drugs all had the effect of inhibiting the activity of monoamine oxidase A, and Jieyu No. 4 and Jieyu No. 2 were better at inhibiting the activity of monoamine oxidase A. The formulas of these two preparations both contained nicotine. It is suggested that the prescription containing nicotine has a stronger inhibitory ability to the activity of monoamine oxidase-A.

本发明按实施例的技术方案配制的电子烟雾化液,经药剂学检测,符合电子烟雾化液的质量要求,经动物实验观察,小白鼠连续吸本发明的电子烟雾化液2个月,每天1次,每次2小时,没有发现毒性反应,对心脏、肺脏及脑组织的病理检查,没有发现有病理形态学的改变。研究表明,本发明技术方案配制的电子烟雾化液对小白鼠连续吸烟2个月不会引起毒性。The electronic smog liquid formulated according to the technical scheme of the embodiment of the present invention meets the quality requirements of the electronic smog liquid through pharmacy testing. Through animal experiment observation, mice continuously inhale the electronic smog liquid of the present invention for 2 months, every day One time, 2 hours each time, no toxic reaction was found, and no pathological changes were found in the pathological examination of the heart, lung and brain tissues. Studies have shown that the electronic cigarette liquid prepared by the technical solution of the present invention will not cause toxicity to mice who smoke continuously for 2 months.

以上所述仅为本发明的较佳实施例,凡依本发明权利要求范围所做的均等变化与修饰,皆应属本发明权利要求的涵盖范围。The above descriptions are only preferred embodiments of the present invention, and all equivalent changes and modifications made according to the scope of the claims of the present invention shall fall within the scope of the claims of the present invention.

Claims (12)

1. The electronic cigarette atomized liquid with the monoamine oxidase activity inhibiting effect is characterized by comprising the following preparation components in parts by weight: 1 to 5 parts of limonene, 1 to 5 parts of linalool, 1 to 5 parts of vanillin, 0.3 to 3 parts of phyllitol, 0.3 to 3 parts of geraniol, 1 to 5 parts of methyl cinnamate, 1 to 5 parts of menthol, 1 to 5 parts of maltol, 1 to 5 parts of benzoic acid, 1 to 5 parts of salvianic acid, 50 to 80 parts of propylene glycol and 10 to 30 parts of glycerin.
2. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 1, wherein the preparation components of the electronic cigarette atomized liquid comprise the following components in parts by weight: 0.1 to 5 portions of nicotine.
3. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 1, wherein the preparation components of the electronic cigarette atomized liquid comprise the following components in parts by weight: 1-5 parts of naringin.
4. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 1, wherein the preparation components of the electronic cigarette atomized liquid comprise the following components in parts by weight: 0.1 to 5 portions of nicotine and 1 to 5 portions of naringin.
5. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 1, wherein 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of phyllitol, 0.5-1.5 parts of geraniol, 1.2-2 parts of methyl cinnamate, 1-3 parts of menthol, 1-2 parts of maltol, 1-2 parts of benzoic acid, 1-2 parts of tanshinol, 71-78 parts of propylene glycol and 11-15 parts of glycerin.
6. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 5, wherein 2.5 parts of limonene, 1.5 parts of linalool, 2 parts of vanillin, 0.5 parts of phyllitol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of salvianic acid, 74.5 parts of propylene glycol and 12.5 parts of glycerin.
7. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 2, wherein 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of phyllitol, 0.5-1.5 parts of geraniol, 1.2-2 parts of methyl cinnamate, 1-3 parts of menthol, 1-2 parts of maltol, 1-2 parts of benzoic acid, 1-2 parts of tanshinol, 71-78 parts of propylene glycol, 11-15 parts of glycerin and 0.2-2 parts of nicotine.
8. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 7, wherein 2.5 parts of limonene, 1.5 parts of linalool, 2 parts of vanillin, 0.5 parts of phyllitol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of salvianic acid, 74 parts of propylene glycol, 12.5 parts of glycerin and 0.5 part of nicotine.
9. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 3, wherein 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of phyllitol, 0.5-1.5 parts of geraniol, 1.2-2 parts of methyl cinnamate, 1-3 parts of menthol, 1-2 parts of maltol, 1-2 parts of benzoic acid, 1-2 parts of tanshinol, 71-78 parts of propylene glycol, 11-15 parts of glycerin and 1-3 parts of naringin.
10. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 9, wherein 2.5 parts of limonene, 1.5 parts of linalool, 2 parts of vanillin, 0.5 parts of phyllitol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of salvianic acid, 74 parts of propylene glycol, 12 parts of glycerin and 1 part of naringin.
11. The electronic cigarette atomized liquid with monoamine oxidase activity inhibiting effect according to claim 4, wherein 2-4 parts of limonene, 1.2-3 parts of linalool, 1.5-3 parts of vanillin, 0.5-2 parts of phyllitol, 0.5-1.5 parts of geraniol, 1.2-2 parts of methyl cinnamate, 1-3 parts of menthol, 1-2 parts of maltol, 1-2 parts of benzoic acid, 1-2 parts of tanshinol, 71-78 parts of propylene glycol, 11-15 parts of glycerin, 0.2-2 parts of nicotine and 1-3 parts of naringin.
12. The electronic cigarette atomized liquid having a monoamine oxidase inhibitory action according to claim 11, wherein 2.5 parts of limonene, 1.5 parts of linalool, 2 parts of vanillin, 0.5 parts of phyllitol, 0.5 parts of geraniol, 1.5 parts of methyl cinnamate, 1.5 parts of menthol, 1 part of maltol, 1 part of benzoic acid, 1 part of salvianic acid, 73.5 parts of propylene glycol, 12 parts of glycerin, 0.5 parts of nicotine and 1 part of naringin.
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