WO2025118385A1 - Nicotine liquid preparation, and preparation method therefor and use thereof - Google Patents

Abstract

A nicotine liquid preparation, and a preparation method therefor and the use thereof. The raw material components of the nicotine liquid preparation comprise nicotine, an additive capable of simulating the head-rush feeling of nicotine, an atomization solvent and an organic acid. The additive capable of simulating the head-rush feeling of nicotine is selected from at least one of cytisine, magnolol and 6-methylnicotine. The nicotine liquid preparation has a nicotine content of 10-20 mg/g.

Description

A nicotine liquid preparation and its preparation method and application

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority of the Chinese patent application filed with the China Patent Office on December 8, 2023, with application number 202311690126.1 and invention name “A nicotine liquid preparation, its preparation method and application”, the entire contents of which are incorporated by reference into this application.

Technical Field

The present application relates to the field of electronic atomization technology, and specifically to a nicotine liquid preparation and a preparation method and application thereof.

Background Art

The electronic atomization system is a smoking-alternative product that delivers nicotine without tobacco smoke. It delivers nicotine into the blood and, like nicotine replacement therapy, can effectively reduce tobacco intake and help smokers quit smoking. The electronic atomization system is mainly composed of three parts: a cartridge, an atomizer, and a power source. The cartridge is a container device for holding nicotine liquid preparations. The main ingredients of nicotine liquid preparations are nicotine, propylene glycol, glycerol, flavors and fragrances, etc. The atomizer is powered by a battery rod and can atomize the liquid nicotine in the cartridge into an aerosol with a specific smell for users to use.

The core ingredient in nicotine liquid preparations is nicotine. When the power source heats the atomizer, the nicotine in the nicotine liquid preparation will be atomized into an aerosol and then inhaled by the human body, thereby bringing people an increase in satisfaction. However, nicotine is highly toxic and addictive. Long-term inhalation will affect human health. In order to prevent the abuse of nicotine and protect the health and safety of the public, countries currently strictly regulate nicotine, and basically limit the nicotine content to 20 mg/g or less. However, a decrease in nicotine content will lead to a decrease in satisfaction. In order to improve consumer satisfaction, the existing technology generally uses low-content nicotine in the form of nicotine salts. The commonly used organic acid to form nicotine salts is benzoic acid. The compounding of benzoic acid and low-content nicotine can improve satisfaction, but the improvement effect is still limited.

Summary of the invention

The purpose of the present application is to overcome the defects in the prior art that nicotine has great toxicity and addictiveness, long-term inhalation will affect human health, and low-content nicotine combined with benzoic acid has limited effect on improving user satisfaction, and further provide a nicotine liquid preparation and its preparation method and application.

In order to achieve the above objectives, this application adopts the following technical solutions:

The present application provides a nicotine liquid preparation, wherein the raw material components of the nicotine liquid preparation include nicotine, a nicotine head feeling simulating additive, an atomizing solvent and an organic acid;

The nicotine head-feeling simulating additive is selected from at least one of cytisine, magnolol, and 6-methylnicotine;

The nicotine content in the nicotine liquid preparation is 10-20 mg/g.

Optionally, the mass ratio of the nicotine head-feeling simulating additive to nicotine is (0.1-3.7):(1-2);

Optionally, the mass ratio of the nicotine head-feeling simulating additive to nicotine is (1-3.7):(1-2).

Optionally, the nicotine head-feeling simulating additives are selected from at least two of cytisine, magnolol, and 6-methylnicotine.

Optionally, the nicotine head-feeling simulating additives are cytisine and magnolol;

The mass ratio of cytisine to magnolol is (1-20): (1-10);

Optionally, the mass of the cytisine accounts for 0.1-2% of the mass of the nicotine liquid preparation;

The mass of magnolol accounts for 0.1-1% of the mass of the nicotine liquid preparation.

Optionally, the nicotine head-feeling simulating additives are cytisine, magnolol and 6-methylnicotine;

The mass ratio of cytisine, magnolol and 6-methylnicotine is (1-20): (1-10): (1-10);

Optionally, the mass of the cytisine accounts for 0.1-2% of the mass of the nicotine liquid preparation;

The mass of magnolol accounts for 0.1-1% of the mass of the nicotine liquid preparation;

The mass of the 6-methyl nicotine accounts for 0.1-1% of the mass of the nicotine liquid preparation.

Optionally, the mass ratio of the atomization solvent to nicotine is (40-97.8):(1-2).

Optionally, the atomizing solvent includes at least one of propylene glycol, glycerol, water, ethanol, triacetin, and sorbitol.

Optionally, the atomizing solvent is propylene glycol and glycerol;

The mass ratio of propylene glycol to glycerol is (1-50):(1-50).

Optionally, the organic acid comprises at least one of C3-C8 organic carboxylic acids;

Optionally, the organic acid includes at least one of C3-C8 monobasic organic carboxylic acid, C3-C8 dibasic organic carboxylic acid, and C3-C8 tribasic organic carboxylic acid.

Optionally, the organic acid includes at least one of salicylic acid, citric acid, malic acid, benzoic acid, levulinic acid, tartaric acid, and succinic acid;

Optionally, the organic acid is benzoic acid.

Optionally, the organic acid is calculated based on the carboxyl group, and the molar ratio of the organic acid to the nicotine is (1-2): (1-2);

Optionally, the organic acid is calculated based on the carboxyl group, and the molar ratio of the organic acid to the nicotine is 1:1.

Optionally, the organic acid is calculated based on carboxyl groups, and the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the molar amount of the organic acid is (0.98-2): (0.98-2);

Optionally, the organic acid is calculated based on carboxyl groups, and the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the molar amount of the organic acid is 1:1.

Optionally, the organic acid is calculated based on the carboxyl group, and the molar ratio of the organic acid to the molar ratio of 6-methylnicotine is (1-2):(1-2).

Optionally, in the nicotine liquid preparation, the nicotine and the organic acid may exist in the form of nicotine organic acid salt, and the 6-methyl nicotine and the organic acid may exist in the form of 6-methyl nicotine organic acid salt.

Optionally, the raw material components of the nicotine liquid preparation further include flavors.

Optionally, the flavor includes at least one of tobacco flavor, fruit flavor, and mint flavor;

Optionally, the fruit flavor includes at least one of blueberry flavor, strawberry flavor, and watermelon flavor.

Optionally, the mass ratio of the flavor to nicotine is (20-50):(1-2).

The nicotine liquid preparation described in the present application is used to enhance the sense of satisfaction, and further, to enhance the smoking experience of consumers.

The present application provides a method for preparing the above-mentioned nicotine liquid preparation, comprising the following steps:

The nicotine, nicotine head-feeling simulating additive, atomizing solvent and organic acid are mixed, and then heated and stirred to obtain the product.

Optionally, the method for preparing the nicotine liquid preparation further comprises the step of adding flavors.

The present application does not specifically limit the stirring method. Optionally, the stirring method is selected from mechanical stirring, mechanical oscillation or ultrasonic oscillation.

The present application provides a use of the above-mentioned nicotine liquid preparation or the nicotine liquid preparation prepared by the above-mentioned preparation method in an atomization device.

Optionally, the atomization device is an electronic atomization device.

Beneficial effects of this application:

The nicotine liquid preparation provided in the present application comprises raw material components including nicotine, a nicotine head-feeling simulating additive, an atomizing solvent and an organic acid; the nicotine head-feeling simulating additive is selected from at least one of cytisine, magnolol and 6-methylnicotine; the nicotine content in the nicotine liquid preparation is 10-20 mg/g. The present application adopts a nicotine head-feeling simulating additive (at least one of cytisine, magnolol and 6-methylnicotine) to make the brain produce a head-feeling effect similar to that of nicotine, which can partially replace the activation effect of nicotine, and adopts a low content (10-20 mg/g) of nicotine to provide a throat hit; specific nicotine head-feeling simulating additives and nicotine The compounded nicotine liquid preparation, due to the synergistic effect of various components, is conducive to improving the user's satisfaction with the low-nicotine liquid preparation, while reducing toxicity and addiction and reducing health damage under the condition of the same smoking experience.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

FIG1 is a normalized heart rate diagram of Example 2, Example 6, Example 12, Example 13 and Comparative Example 1 of the present application;

Figure 2 is an average normalized heart rate graph of Example 2, Example 6, Example 12, Example 13 and Comparative Example 1 of the present application.

DETAILED DESCRIPTION

The following examples are provided for a better understanding of the present application, but are not limited to the best implementation mode described, and do not limit the content and protection scope of the present application. Any product identical or similar to the present application obtained by anyone under the inspiration of the present application or by combining the features of the present application with other prior arts shall fall within the protection scope of the present application.

If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

The core ingredient in nicotine liquid preparations is nicotine. When the power source heats the atomizer, the nicotine in the nicotine liquid preparation will be atomized into an aerosol and then inhaled by the human body. Part of the aerosol is transmitted to the throat, where acetylcholine receptors are also distributed. The nicotine deposited in the throat can bind to the acetylcholine receptors, causing a throat hit. Another part of the aerosol will enter the lungs to participate in the pulmonary venous circulation, and then enter the arterial circulation, quickly transmitting nicotine to the brain, combining with the acetylcholine receptors in the brain, and promoting the brain to release neurotransmitters (dopamine). Dopamine release is a pleasant experience that will enhance the brain's reward function, produce a sense of being high, and make smokers feel satisfied. Satisfaction is a comprehensive evaluation of the feeling of being high and the feeling of throat hit. A suitable throat hit helps to improve the overall satisfaction, but if the throat hit is too strong, it will cause excessive suction irritation and physiological discomfort, which will reduce satisfaction. Nicotine is highly toxic and addictive. Long-term inhalation can affect human health. In order to prevent the abuse of nicotine and protect the health and safety of the public, countries currently have strict regulations on nicotine in e-cigarette products, limiting the nicotine content to 20 mg/g or less. However, the decrease in nicotine content will lead to a decrease in satisfaction. In order to improve consumer satisfaction, the existing technology generally uses nicotine in the form of nicotine salts. The commonly used organic acid to form nicotine salts is benzoic acid. The satisfaction is improved by compounding nicotine and benzoic acid, but the improvement effect is still limited.

Cytisine is a leguminous plant extract that has been shown to have a high affinity for the α4β2 subtype of nicotinic acetylcholine receptors and is a low nonspecific partial agonist. The inventors found that cytisine can interact with acetylcholine receptors in the brain to produce an activation effect similar to nicotine, and synergize with nicotine to improve satisfaction.

Magnolol is the active ingredient in Magnolia officinalis plant extract, which has sedative, hypnotic, antianxiety and anti-epileptic effects. Magnolol can increase the ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) in the frontal cortex, striatum and nucleus accumbens, inhibit the increase of serum corticosterone levels, reverse the decrease of platelet adenylate cyclase activity induced by chronic mild stress (CMS), and play an antidepressant role. Magnolol can counteract the inhibition of endogenous enkephalin release by exogenous morphine, and produce the effect of relieving withdrawal symptoms. Magnolol can also counteract the excitatory effects of central excitatory neurotransmitters glutamate and N-methyl-D-aspartate (NMDA) by promoting the release of β-endorphin and stimulating cannabinoid receptors. Magnolol mainly counteracts the damage of excitatory neurotransmitters to nerve cells by promoting the biosynthesis of γ-aminobutyric acid (GABA), increasing the content of GABA, and enhancing the binding of GABA to receptors.

6-Methylnicotine (CAS: 13270-56-9) is an organic intermediate and a nicotine analog. It is reported that the affinity of nicotine analogs to nicotinic acetylcholine receptors (nAChR) is related to the lipophilicity of the 6-substituent. Related studies have further shown that as the size of the substituent increases, the affinity decreases. The affinity of nicotine analogs is determined by the lipophilicity of the 6-substituent and is also related to the size of the substituent. Among them, the 6-substituent of 6-methylnicotine has the smallest volume, strong lipophilicity, and strong affinity with nAChR receptors, and has a good prospect for medicinal use.

The inventor unexpectedly discovered that compounding nicotine with a nicotine head-simulating additive (at least one of cytisine, magnolol, and 6-methylnicotine) can synergize with the nicotine head-simulating additive, which is beneficial for improving the user's satisfaction when the nicotine content is not higher than 20 mg/g.

The present application provides a nicotine liquid preparation, the raw material components of which include nicotine, a nicotine head-feeling simulating additive, an atomizing solvent and an organic acid; the nicotine head-feeling simulating additive is selected from at least one of cytisine, magnolol and 6-methylnicotine; the nicotine content in the nicotine liquid preparation is 10-20 mg/g. The present application uses a nicotine head-feeling simulating additive (at least one of cytisine, magnolol and 6-methylnicotine) to make the brain produce a head-feeling effect similar to that of nicotine, which can partially replace the activation effect of nicotine, and use a low content (10-20 mg/g) of nicotine to provide a throat hit; the nicotine liquid preparation formed by the compounding of a specific nicotine head-feeling simulating additive and nicotine, under the synergistic effect of each component, is conducive to improving the user's satisfaction with the low-nicotine content liquid preparation, and reduces toxicity and addiction under the condition of the same experience, and reduces Health damage. Optionally, in some optional embodiments, the nicotine content in the nicotine liquid preparation is 10 mg/g, 11 mg/g, 12 mg/g, 13 mg/g, 14 mg/g, 15 mg/g, 16 mg/g, 17 mg/g, 18 mg/g, 19 mg/g, 20 mg/g.

In some optional embodiments, the mass ratio of the nicotine head-feeling simulation additive to nicotine is (0.1-3.7):(1-2); for example, the mass ratio of the nicotine head-feeling simulation additive to nicotine can be selected to be 0.1:1, 0.2:1, 0.3:1, 0.5:1, 0.7:1, 0.9:1, 1:1, 1.3:1, 1.4:1, 1.5:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.1:1, 2.3:1, 2.5:1, 2.8:1, 3:1, 3.1:1, 3.3:1, 3.4:1, 3.5:1, 3.7:1, 0.1:1.25, 0.2:1.25, 0.3:1 .25, 0.5:1.25, 0.7:1.25, 0.9:1.25, 1:1.25, 1.3:1.25, 1.4:1.25, 1.5:1.25, 1.7:1.25, 1.8:1.25, 1.9:1.25, 2:1.25, 2.1:1.25, 2.3:1.25, 2.5:1.25, 2.8:1.25, 3:1.25, 3.1:1.25, 3.3:1.25, 3.4:1.25, 3.5:1.25, 3.7:1.25, 0.1:1.5, 0.2:1.5, 0.3:1.5, 0.5:1.5, 0.7:1.5, 0.9:1.5, 1:1.5 , 1.3:1.5, 1.4:1.5, 1.5:1.5, 1.7:1.5, 1.8:1.5, 1.9:1.5, 2:1.5, 2.1:1.5, 2.3:1.5, 2.5:1.5, 2.8:1.5, 3:1.5, 3.1:1.5, 3.3:1.5, 3.4:1.5, 3.5:1.5, 3.7:1.5, 0.1:1.75, 0.2:1.75, 0.3:1.75, 0.5:1.75, 0.7:1.75, 0.9:1.75, 1:1.75, 1.3:1.75, 1.4:1.75, 1.5:1.75, 1.7:1.75, 1.8:1.75, 1 .9:1.75, 2:1.75, 2.1:1.75, 2.3:1.75, 2.5:1.75, 2.8:1.75, 3:1.75, 3.1:1.75, 3.3:1.75, 3.4:1.75, 3.5:1.75, 3.7:1.75, 0.1:2, 0.2:2, 0.3:2, 0.5:2, 0.7:2, 0.9:2, 1:2, 1.3:2, 1.4:2, 1.5:2, 1.7:2, 1.8:2, 1.9:2, 2:2, 2.1:2, 2.3:2, 2.5:2, 2.8:2, 3:2, 3.1:2, 3.3:2, 3.4:2, 3.5:2, 3.7:2. Optionally, the mass ratio of the nicotine head-simulating additive to nicotine is (1-3.7):(1-2). The inventors found that by controlling the mass ratio of the nicotine head-simulating additive to nicotine within the range of (1-3.7):(1-2), the user's satisfaction is further improved under their synergistic effect.

In some optional embodiments, the nicotine head feeling simulating additive is selected from at least two of cytisine, magnolol, and 6-methylnicotine. The inventors found that when the nicotine head feeling simulating additive is selected from at least two of cytisine, magnolol, and 6-methylnicotine, the satisfaction of the user is more significantly improved than when only one of the nicotine head feeling simulating additives is selected, and can even reach or exceed the satisfaction of the nicotine liquid preparation with benzoic acid as the organic acid and a nicotine content of 30 mg/g on the market.

In some optional embodiments, the nicotine head feeling simulating additive is cytisine and magnolol; the mass ratio of cytisine and magnolol is (1-20): (1-10); for example, cytisine and magnolol can be selected. The mass ratio of magnolol is 1:1, 3:1, 4:1, 5:1, 7:1, 8:1, 9:1, 10:1, 11:1, 13:1, 15:1, 17:1, 19:1, 20:1, 1:3, 3:3, 4:3, 5:3, 7:3, 8:3, 9:3, 10:3, 11:3, 13:3, 15:3, 17:3, 19:3, 20:3, 1:5, 3:5, 4:5, 5:5, 7:5, 8:5, 9:5, 10:5, 1 1:5, 13:5, 15:5, 17:5, 19:5, 20:5, 1:7, 3:7, 4:7, 5:7, 7:7, 8:7, 9:7, 10:7, 11:7, 13:7, 15:7, 17:7, 19:7, 20:7, 1:10, 3:10, 4:10, 5:10, 7:10, 8:10, 9:10, 10:10, 11:10, 13:10, 15:10, 17:10, 19:10, 20:10. Optionally, the mass of the cytisine accounts for 0.1-2% of the mass of the nicotine liquid preparation; the mass of the magnolol accounts for 0.1-1% of the mass of the nicotine liquid preparation. For example, it can be selected that the mass of cytisine accounts for 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2% of the mass of the nicotine liquid preparation; the mass of magnolol accounts for 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1% of the mass of the nicotine liquid preparation.

In some optional embodiments, the nicotine head-feeling simulating additive is cytisine, magnolol and 6-methylnicotine; the inventors found that when the nicotine head-feeling simulating additive is selected from cytisine, magnolol and 6-methylnicotine and they are used together in a synergistic manner, the user's satisfaction is most significantly improved, and the user's satisfaction can even reach the satisfaction of a nicotine liquid preparation on the market with benzoic acid as the organic acid and a nicotine content of 50 mg/g. Under the condition of the same experience, the toxicity and addictiveness can be effectively reduced, and health damage can be reduced. The mass ratio of cytisine, magnolol and 6-methylnicotine is (1-20): (1-10): (1-10); for example, the mass ratio of cytisine and magnolol can be selected as 1:1:1, 3:1:2, 4:1:1, 5:1:5, 7:1:9, 8:1:10, 9:1:1, 10:1:9, 11:1:1, 13:1:6, 15:1:6, 17:1:2, 19:1:1, 20:1:9, 1:3, 3:3:1, 4:3:1, 5:3:4, 7:3:6, 8:3:1, 9:3:8, 10:3:10, 11:3:10, 13:3:3, 15:3:1, 17:3:9, 19:3:2, 20:3:10, 1:5:1, 3:5:10, 4:5:2, 5:5:5 ,7:5:6,8:5:9,9:5:10,10:5:1,11:5:6,13:5:9,15:5:10,17:5:8,19:5:8,20:5:9,1:7:8,3:7:9,4:7:10,5:7:10,7:7:1,8:7:1,9:7:2,10:7:10,11:7:9,13:7:10, 15:7:1, 17:7:1, 19:7:10, 20:7:5, 1:10:1, 3:10:2, 4:10:10, 5:10:10, 7:10:1, 8:10:5, 9:10:9, 10:10:5, 11:10:4, 13:10:3, 15:10:7, 17:10:10, 19:10:8, 20:10:8. Optionally, the mass of the cytisine accounts for 0.1-2% of the mass of the nicotine liquid preparation; the mass of the magnolol accounts for 0.1-1% of the mass of the nicotine liquid preparation; the mass of the 6-methylnicotine accounts for 0.1-1% of the mass of the nicotine liquid preparation. For example, it can be selected that the mass of the cytisine accounts for 0.1-2% of the mass of the nicotine liquid preparation. The mass of magnolol accounts for 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, and 2% of the mass of the nicotine liquid preparation; the mass of magnolol accounts for 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, and 1% of the mass of the nicotine liquid preparation; the mass of 6-methylnicotine accounts for 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, and 1% of the mass of the nicotine liquid preparation.

In some optional embodiments, the atomizing solvent may be a conventional atomizing solvent in the art, including but not limited to at least one of propylene glycol, glycerol, water, ethanol, triacetin, and sorbitol; optionally, the mass ratio of the atomizing solvent to nicotine is (40-97.8):(1-2), for example, the mass ratio of the atomizing solvent to nicotine that can be selected is 40:1, 45:1, 47:1, 50:1, 60:1, 70:1, 80:1, 90:1, 97.8:1, 40:1.5, 45:1.5, 47:1.5, 50:1.5, 60:1.5, 70:1.5, 80:1.5, 90:1.5, 97.8:1.5, 40:2, 45:2, 47:2, 50:2, 60:2, 70:2, 80:2, 90:2, 97.8:2. Optionally, the atomizing solvent is propylene glycol and glycerol. The mass ratio of propylene glycol to glycerol is (1-50): (1-50), for example, the mass ratio of propylene glycol to glycerol can be selected as 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:13, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 2:1, 2:3, 2:5, 2:7, 2:9, 2:1 0, 2:13, 2:15, 2:20, 2:25, 2:30, 2:35, 2:40, 2:45, 2:50, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 12:1, 13:1, 15:1, 18:1, 20:1, 22:1, 25:1, 29:1, 30:1, 32:1, 35:1, 40:1, 43:1, 45:1, 47:1, 50:1. The addition of the atomizing solvent in the present application can better dissolve the raw material components, effectively improve the atomization efficiency of nicotine, and increase satisfaction.

In some optional embodiments, the atomization solvent is propylene glycol, glycerol and ethanol. For example, the mass ratio of propylene glycol, glycerol and ethanol can be selected to be (1-50): (1-50): (1-2).

In some optional embodiments, the organic acid includes at least one of C3-C8 organic carboxylic acids; further optionally, the organic acid includes at least one of C3-C8 monobasic organic carboxylic acids, C3-C8 dibasic organic carboxylic acids, and C3-C8 tribasic organic carboxylic acids. Further optionally, the organic acid includes at least one of salicylic acid, citric acid, malic acid, benzoic acid, levulinic acid, tartaric acid, and succinic acid; further optionally, the organic acid is benzoic acid. The present application can further ensure the user's satisfaction by further adding a specific organic acid to the raw material components to form a nicotine salt.

In some optional embodiments, the organic acid is calculated based on the carboxyl group, and the molar amount ratio of the organic acid to the nicotine is (1-2): (1-2); for example, the organic acid can be selected based on the carboxyl group, and the molar amount ratio of the organic acid to the nicotine is 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 1:1.2, 1.1:1.2, 1.2:1.2, 1.3:1.2, 1.4:1.2, 1.5:1.2, 1.6:1.2, 1.7:1.2, 1.8:1.2, 1.9:1.2, 2:1.2, 1:1.5, 1.1:1.5, 1.2:1.5, 1.3:1.5, 1.4:1.5, 1.5:1.5, 1.6:1.5, 1.7:1.5, 1.8 : 1.5, 1.9:1.5, 2:1.5, 1:1.7, 1.1:1.7, 1.2:1.7, 1.3:1.7, 1.4:1.7, 1.5:1.7, 1.6:1.7, 1.7:1.7, 1.8:1.7, 1.9:1.7, 2:1.7, 1:2, 1.1:2, 1.2:2, 1.3:2, 1.4:2, 1.5:2, 1.6:2, 1.7:2, 1.8:2, 1.9:2, 2:2. After adding the synergistic substance nicotine head feeling simulation additive, the inventor further found that the amount of organic acid added will affect the sense of satisfaction. Benzoic acid and nicotine will combine to form a salt state. Changing the molar ratio of organic acid and nicotine can change the acid-base environment of the throat, affecting the strength of the throat hit during the aerosol entering the lungs. The inventors have found that when the molar ratio of the organic acid to the nicotine is (1-2):(1-2), the feeling of being high and the feeling of hitting the throat during inhalation will change, and the overall satisfaction will be high.

In some optional embodiments, the organic acid is calculated based on the carboxyl group, and the molar amount ratio of the organic acid to the 6-methylnicotine is (1-2): (1-2); for example, it can be selected that the organic acid is calculated based on the carboxyl group, and the molar amount ratio of the organic acid to the 6-methylnicotine is 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 1:1.2, 1.1:1.2, 1.2:1.2, 1.3:1.2, 1.4:1.2, 1.5:1.2, 1.6:1.2, 1.7:1.2, 1.8:1.2, 1.9:1.2, : 2, 1.1:2, 1.2:2, 1.3:2, 1.4:2, 1.5:2, 1.6:2, 1.7:2, 1.8:2, 1.9:2, 2:2.

In some optional embodiments, the organic acid is calculated based on carboxyl groups, and the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the organic acid is (0.98-2): (0.98-2). For example, it can be selected that the organic acid is calculated based on carboxyl groups, and the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the organic acid is 0.98:0.99, 0.99:0.98, 0.98:1, 0.99:1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9 :1, 2:1, 0.98:1.2, 0.99:1.2, 1:1.2, 1.1:1.2, 1.2:1.2, 1.3:1.2, 1.4:1.2, 1.5:1.2, 1.6:1.2, 1.7:1.2, 1.8:1.2, 1.9:1.2, 2:1.2, 0.98:1.5, 0.99:1.5, 1:1.5, 1. 1:1.5, 1.2:1.5, 1.3:1.5, 1.4:1.5, 1.5:1.5, 1.6:1.5, 1.7:1.5, 1.8:1.5, 1.9:1.5, 2:1.5, 0.98:1.7, 0.99:1.7, 1:1.7, 1.1:1.7, 1.2:1.7, 1.3:1.7, 1.4:1.7, 1.5 : 1.7, 1.6:1.7, 1.7:1.7, 0.98:1.8, 0.99:1.8, 1.8:1.7, 1.9:1.7, 2:1.7, 0.98:2, 0.99:2, 1:2, 1.1:2, 1.2:2, 1.3:2, 1.4:2, 1.5:2, 1.6:2, 1.7:2, 1.8:2, 1.9:2, 2: 2. After adding the synergistic substance nicotine head-hitting additive, the inventors further found that the amount of organic acid added will affect the sense of satisfaction. Nicotine and 6-methylnicotine will combine with benzoic acid to form a salt state. Changing the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the organic acid can change the acid-base environment of the throat and affect the strength of the throat hit during the aerosol entering the lungs. The inventors found that when the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the organic acid is (0.98-2) based on the carboxyl group of the organic acid: (0.98-2), the head and throat hit during inhalation will change, and the overall sense of satisfaction is high.

In some optional embodiments, the raw material components of the nicotine liquid preparation also include flavors. The flavors may be conventional existing flavor materials in the art, which may be commercially available or prepared by conventional preparation methods. For example, they may be selected from monomeric flavor raw materials or a variety of extracts. Including but not limited to tobacco flavors, fruit flavors, and mint flavors. Furthermore, the fruit flavors include at least one of blueberry flavors, strawberry flavors, and watermelon flavors; optionally, the mass ratio of the flavor to nicotine is (20-50): (1-2), for example, the mass ratio of the flavor to nicotine may be selected to be 20:1, 22:1, 25:1, 27:1, 30:1, 32:1, 35:1, 37:1, 39:1, 40:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79:1, 80:1, 81:1, 82:1 :1, 45:1, 47:1, 49:1, 50:1, 20:1.2, 22:1.2, 25:1.2, 27:1.2, 30:1.2, 32:1.2, 35:1.2, 37:1.2, 39:1.2, 40:1.2, 42:1.2, 45:1.2, 47:1.2, 49:1.2, 50:1.2, 20:1.5, 22: 1.5, 25:1.5, 27:1.5, 30:1.5, 32:1.5, 35:1.5, 37:1.5, 39:1.5, 40:1.5, 42:1.5, 45:1.5, 47:1.5, 49:1.5, 50:1.5, 20:1.7, 22:1.7, 25:1.7, 27:1.7, 30:1.7, 32:1.7, 35:1.7, 37:1.7, 39:1.7, 40:1.7, 42:1.7, 45:1.7, 47:1.7, 49:1.7, 50:1.7, 20:2, 22:2, 25:2, 27:2, 30:2, 32:2, 35:2, 37:2, 39:2, 40:2, 42:2, 45:2, 47:2, 49:2, 50:2.

The present application also provides a method for preparing the above-mentioned nicotine liquid preparation, comprising the following steps: mixing nicotine, a nicotine head-feeling simulating additive, an atomizing solvent and an organic acid, and then heating and stirring the mixture to obtain the nicotine liquid preparation.

In some optional embodiments, the method for preparing the nicotine liquid preparation further comprises the step of adding flavors.

The present application does not impose any specific restrictions on the heating and stirring temperature and time, as long as the raw materials can be dissolved. Optionally, the dissolution temperature is not higher than 100°C. Optionally, the heating and stirring temperature is 40-65°C, and the heating and stirring time is 20-30min. In the present application, all the raw materials can be mixed and then heated to dissolve, or some of the raw materials can be mixed and dissolved first, and then the remaining raw materials can be mixed and dissolved. In some optional embodiments, the preparation method of the nicotine liquid preparation includes the following steps: mixing nicotine, a nicotine head-simulating additive, an organic acid and an atomizing solvent, heating at 40-65°C for 20-30 minutes to dissolve and mix evenly, and then adding fragrance at 10-40°C. The mixture is stirred for 5-40 minutes to be uniformly mixed to obtain the nicotine liquid preparation.

The present application also provides a use of the above-mentioned nicotine liquid preparation or the nicotine liquid preparation prepared by the above-mentioned preparation method in an atomization device. Optionally, the atomization device is an electronic atomization device.

Example 1

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine, 1.50 g of benzoic acid, 0.1 g of cytisine, 0.3 g of magnolol, 11.1 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 2

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine, 1.50 g of benzoic acid, 0.7 g of cytisine, 0.3 g of magnolol, 10.5 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 3

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine, 1.50 g of benzoic acid, 1.5 g of cytisine, 0.3 g of magnolol, 9.7 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 4

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine, 1.50 g of benzoic acid, 2 g of cytisine, 0.3 g of magnolol, 9.2 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 5

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine, 1.50 g of benzoic acid, 2.0 g of cytisine, 1 g of magnolol, 8.5 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 6

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine was mixed with 1.50 g of benzoic acid, 0.4 g of cytisine, 0.3 g of magnolol, 0.3 g of 6-methylnicotine, 10.5 g of propylene glycol and 40 g of glycerol, and heated and stirred in a 60°C water bath for 20 min to dissolve and mix evenly. After cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 7

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

1.5 g of nicotine, 1.48 g of benzoic acid, 0.7 g of cytisine, 0.3 g of magnolol, 0.5 g of 6-methylnicotine, 10.52 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60°C water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 8

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

1.3 g of nicotine, 1.48 g of benzoic acid, 0.7 g of cytisine, 0.3 g of magnolol, 0.7 g of 6-methylnicotine, 10.52 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60°C water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 9

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

1.3 g of nicotine, 1.46 g of benzoic acid, 1.5 g of cytisine, 0.3 g of magnolol, 0.7 g of 6-methylnicotine, 9.74 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60°C water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 10

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

1.3 g of nicotine, 1.46 g of benzoic acid, 2.0 g of cytisine, 1.0 g of magnolol, 0.7 g of 6-methylnicotine, 8.54 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60°C water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Embodiment 11

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

1.0g nicotine, 1.45g benzoic acid, 1.5g cytisine, 0.3g magnolol, 1.0g 6-methylnicotinic acid 45 g of blueberry flavor was added after cooling to room temperature, and the mixture was stirred for 20 minutes to obtain the nicotine liquid preparation.

Example 12

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine, 1.50 g of benzoic acid, 1 g of cytisine, 10.5 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Example 13

This embodiment provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2 g of nicotine, 1.50 g of benzoic acid, 1 g of magnolol, 10.5 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Comparative Example 1

This comparative example provides a method for preparing a nicotine liquid preparation, comprising the following steps:

2.0 g of nicotine, 1.50 g of benzoic acid, 11.5 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Comparative Example 2

This comparative example provides a method for preparing a nicotine liquid preparation, comprising the following steps:

3.0 g of nicotine, 2.26 g of benzoic acid, 9.74 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and after cooling to room temperature, 45 g of blueberry flavor was added, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Comparative Example 3

This comparative example provides a method for preparing a nicotine liquid preparation, comprising the following steps:

4.0 g of nicotine, 3 g of benzoic acid, 8.0 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and 45 g of blueberry flavor was added after cooling to room temperature, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Comparative Example 4

This comparative example provides a method for preparing a nicotine liquid preparation, comprising the following steps:

5.0 g of nicotine, 3.76 g of benzoic acid, 6.24 g of propylene glycol and 40 g of glycerol were mixed, heated and stirred in a 60° C. water bath for 20 min to dissolve and mix evenly, and 45 g of blueberry flavor was added after cooling to room temperature, and stirring was continued for 20 min to mix evenly to obtain the nicotine liquid preparation.

Test Case

This application uses a subjective smoking method to score various smoking indicators of the nicotine liquid preparations of Examples 1-13 and Comparative Examples 1-4. The smoking team consists of 12 people, all of whom have more than 5 years of traditional cigarette or more than 3 years of electronic cigarette smoking experience, and have undergone nicotine withdrawal 12 hours before smoking.

Each smoke taster is given a smoke taste evaluation form, and a blind scoring method is adopted. Different embodiments and comparative examples are randomly coded by 3-digit numbers. The evaluator starts smoking at 10 am and smokes the next random sample after an interval of one hour. The smoking method is: during the smoking process of one sample, the smoke taster takes a total of 8 puffs (3 seconds per puff, 27 seconds between each puff), the smoke stays in the mouth for a while, and then swallows the smoke into the lungs. The smoke tasters cannot communicate their feelings about smoking, and each scores and evaluates according to the evaluation indicators in Table 1, and writes down their own smoking results on the smoking evaluation form. The test results are shown in Table 2 (the scoring value is the average score).

Table 1 Evaluation indicators

Table 2 Product absorption scoring data

The nicotine liquid preparations prepared in Example 2, Example 6, Example 12, Example 13 and Comparative Example 1 (hereinafter referred to as samples) were tested for heart rate during the smoking process. The test method is: the smoking personnel perform nicotine withdrawal the night before the smoking test, and the heart rate test during the smoking process is performed at 9 am on the day of smoking. Before smoking, wear the heart rate test instrument (the heart rate test instrument is Lepu Xinanbao ER1), and monitor the real-time changes of the heart rate throughout the smoking process. After the heart rate instrument is worn and debugged, a 2-minute baseline heart rate test is performed. After the heart rate stabilizes, the heart rate monitoring of the smoking process begins, using the RELX5 cigarette rod (with samples of different embodiments and comparative examples), and a total of 5 puffs of smoke are inhaled (3s per puff, 27s between adjacent puffs), the whole smoking time is about 2.5min, and the time when each puff of smoke starts is recorded. After the smoking is completed, the heart rate changes are monitored for another 1min, and then the experiment is terminated. After finishing one sample, abstain for 2 hours before testing the heart rate during the next sample. The test results are shown in Figures 1 and 2, where the normalized heart rate in Figure 1 is the ratio of the real-time monitored heart rate during the smoking process to the average baseline heart rate within the above 2 minutes, and the average normalized heart rate in Figure 2 is the ratio of the average monitored heart rate during the smoking process to the average baseline heart rate.

Obviously, the above embodiments are only examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For ordinary technicians in the relevant field, other different forms of changes can be made based on the above description. It is not necessary and impossible to list all the embodiments here. However, the obvious changes or modifications derived therefrom are still within the protection scope of the invention.

Claims (19)

A nicotine liquid preparation, characterized in that the raw material components of the nicotine liquid preparation include nicotine, a nicotine head feeling simulating additive, an atomizing solvent and an organic acid; The nicotine head-feeling simulating additive is selected from at least one of cytisine, magnolol, and 6-methylnicotine; The nicotine content in the nicotine liquid preparation is 10-20 mg/g. The nicotine liquid preparation according to claim 1, characterized in that the mass ratio of the nicotine head-feeling simulating additive to nicotine is (0.1-3.7):(1-2); Optionally, the mass ratio of the nicotine head-feeling simulating additive to nicotine is (1-3.7):(1-2). The nicotine liquid preparation according to claim 1 or 2, characterized in that the nicotine head feeling simulating additive is selected from at least two of cytisine, magnolol, and 6-methylnicotine. The nicotine liquid preparation according to any one of claims 1 to 3, characterized in that the nicotine head feeling simulating additive is cytisine and magnolol; The mass ratio of cytisine to magnolol is (1-20): (1-10); Optionally, the mass of the cytisine accounts for 0.1-2% of the mass of the nicotine liquid preparation; The mass of magnolol accounts for 0.1-1% of the mass of the nicotine liquid preparation. The nicotine liquid preparation according to any one of claims 1 to 3, characterized in that the nicotine head feeling simulating additive is cytisine, magnolol and 6-methyl nicotine; The mass ratio of cytisine, magnolol and 6-methylnicotine is (1-20): (1-10): (1-10); Optionally, the mass of the cytisine accounts for 0.1-2% of the mass of the nicotine liquid preparation; The mass of magnolol accounts for 0.1-1% of the mass of the nicotine liquid preparation; The mass of the 6-methyl nicotine accounts for 0.1-1% of the mass of the nicotine liquid preparation. The nicotine liquid preparation according to any one of claims 1 to 5, characterized in that the mass ratio of the atomizing solvent to nicotine is (40-97.8):(1-2). The nicotine liquid preparation according to any one of claims 1 to 6, characterized in that the atomization solvent comprises at least one of propylene glycol, glycerol, water, ethanol, triacetin, and sorbitol. The nicotine liquid preparation according to any one of claims 1 to 7, characterized in that the atomization solvent is propylene glycol and glycerol; The mass ratio of propylene glycol to glycerol is (1-50):(1-50). The nicotine liquid preparation according to any one of claims 1 to 8, characterized in that the organic acid comprises at least one of C3-C8 organic carboxylic acids; Optionally, the organic acid includes at least one of C3-C8 monobasic organic carboxylic acid, C3-C8 dibasic organic carboxylic acid, and C3-C8 tribasic organic carboxylic acid. The nicotine liquid preparation according to any one of claims 1 to 9, characterized in that the organic acid comprises at least one of salicylic acid, citric acid, malic acid, benzoic acid, levulinic acid, tartaric acid, and succinic acid; Optionally, the organic acid is benzoic acid. The nicotine liquid preparation according to any one of claims 1 to 10, characterized in that, the organic acid is calculated based on the carboxyl group, and the molar amount ratio of the organic acid to the nicotine is (1-2): (1-2); Optionally, the organic acid is calculated based on the carboxyl group, and the molar ratio of the organic acid to the nicotine is 1:1. The nicotine liquid preparation according to any one of claims 1 to 10, characterized in that, the organic acid is calculated based on carboxyl groups, and the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the molar amount of the organic acid is (0.98-2): (0.98-2); Optionally, the organic acid is calculated based on carboxyl groups, and the molar ratio of the total molar amount of nicotine and 6-methylnicotine to the molar amount of the organic acid is 1:1. The nicotine liquid preparation according to any one of claims 1 to 12, characterized in that the raw material components of the nicotine liquid preparation further include flavors. The nicotine liquid preparation according to claim 13, characterized in that the flavor comprises at least one of tobacco flavor, fruit flavor, and mint flavor; Optionally, the fruit flavor includes at least one of blueberry flavor, strawberry flavor, and watermelon flavor. The nicotine liquid preparation according to any one of claims 13-14, characterized in that the mass ratio of the flavor to nicotine is (20-50):(1-2). A method for preparing the nicotine liquid preparation according to any one of claims 1 to 15, characterized in that it comprises the following steps: The nicotine, nicotine head-feeling simulating additive, atomizing solvent and organic acid are mixed, and then heated and stirred to obtain the product. The method for preparing the nicotine liquid preparation according to claim 16, further comprising the step of adding flavoring. Use of the nicotine liquid preparation according to any one of claims 1 to 15 or the nicotine liquid preparation prepared by the preparation method according to any one of claims 16 or 17 in an atomization device. The use according to claim 18 is characterized in that the atomization device is an electronic atomization device.