Disclosure of Invention
The invention aims to overcome the defects that a zero-nicotine atomization preparation in the prior art has no throat-hitting feel and head-up feel caused by nicotine, and a product is weak in satisfaction and cannot enable a consumer to physiologically separate addiction, and further provides a nicotine substitution liquid preparation and a preparation method and application thereof.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the invention provides a nicotine replacement liquid preparation, which comprises the raw material components of a nicotine throat feeling simulation additive, a nicotine upper head feeling simulation additive and an atomization solvent;
The nicotine throat feeling simulation additive is at least one selected from piperine and 6-methyl nicotine;
the nicotine upper sense simulation additive is at least one selected from cytisine, magnolol and 6-methyl nicotine.
Preferably, the total mass content of the nicotine throat feel simulation additive and the nicotine upper head feel simulation additive in the nicotine substitution liquid preparation is 2.1-61mg/g.
Preferably, the mass ratio of the nicotine throat feel simulation additive to the nicotine upper head feel simulation additive is (0.1-11): 2-50.
Preferably, the raw material components of the nicotine replacement liquid preparation comprise 6-methyl nicotine and an atomization solvent.
Preferably, the mass ratio of the 6-methyl nicotine to the atomized solvent is (0.3-5): 40-95.
Preferably, the raw material components of the nicotine replacement liquid preparation comprise a nicotine throat feel simulation additive, a nicotine upper head feel simulation additive and an atomization solvent;
The nicotine throat feeling simulation additive is at least one selected from piperine and 6-methyl nicotine;
the nicotine upper feeling simulation additive is at least one selected from cytisine and magnolol.
Preferably, when the nicotine throat-feel simulating additive is piperine, the nicotine upper-feel simulating additive is cytisine and/or magnolol;
or when the nicotine throat feel simulation additive is 6-methyl nicotine, the nicotine upper head feel simulation additive is cytisine and/or magnolol.
Preferably, when the nicotine throat-feeling simulation additive is piperine, the nicotine upper head-feeling simulation additive is cytisine and magnolol, and the mass ratio of the cytisine to the magnolol is (5-40): 5-30;
Or when the nicotine throat feeling simulation additive is 6-methyl nicotine, the nicotine upper head feeling simulation additive is cytisine and magnolol, and the mass ratio of the cytisine to the magnolol is (1-25) (1-5).
Preferably, the ratio of the total mass of the nicotine throat feel simulation additive and the nicotine upper head feel simulation additive to the mass of the atomized solvent is (0.3-5): 40-95.
Preferably, the atomizing solvent comprises at least one of propylene glycol and glycerol.
Preferably, the atomizing solvent is propylene glycol and glycerol;
the mass ratio of the propylene glycol to the glycerol is (1-50) to (1-50).
Preferably, the mass content of the nicotine throat feeling simulation additive in the nicotine substitution liquid preparation is 0.1-11mg/g, and the mass content of the nicotine upper head feeling simulation additive is 2-50mg/g;
preferably, the raw material component of the nicotine replacement liquid preparation further comprises an organic acid.
Preferably, the organic acid comprises at least one of a C3-C8 organic carboxylic acid;
Optionally, the organic acid comprises at least one of a C3-C8 mono-organic carboxylic acid, a C3-C8 di-organic carboxylic acid, and a C3-C8 tri-organic carboxylic acid.
Preferably, 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.
Preferably, the molar amount of the organic acid and the molar amount of the 6-methyl nicotine are in a ratio of 1 (0.98-1.5) based on carboxyl groups;
Preferably, the molar amount of the organic acid to the molar amount of 6-methylnicotine is 1:1, calculated as carboxyl groups.
Preferably, the raw material components of the nicotine replacement liquid preparation further comprise essence.
Preferably, the essence comprises at least one of tobacco essence, fruit essence and mint essence;
Optionally, the fruit essence comprises at least one of mango essence, blueberry essence and grape essence.
Preferably, the mass ratio of the total mass of the nicotine throat feel simulation additive and the nicotine upper head feel simulation additive to the essence is (0.3-5) (20-45).
The nicotine replacement liquid preparation is used for improving satisfaction, and further is used for improving satisfaction of consumers.
The invention provides a preparation method of a nicotine replacement liquid preparation according to the claims, which comprises the following steps:
Mixing nicotine throat feeling simulation additive, nicotine upper head feeling simulation additive and atomized solvent, heating, and stirring.
Preferably, the method for preparing the nicotine replacement liquid preparation further comprises the step of adding essence.
Preferably, the method for preparing the nicotine replacement liquid preparation further comprises the step of adding an organic acid.
The stirring mode is not particularly limited in the invention, and the stirring mode is selected from mechanical stirring, mechanical oscillation or ultrasonic oscillation.
The invention provides an application of the nicotine replacement liquid preparation or the nicotine replacement liquid preparation prepared by the preparation method in an atomization device.
Preferably, the atomization device is an electronic atomization device.
The invention has the beneficial effects that:
The nicotine replacement liquid preparation comprises a nicotine throat feeling simulation additive, a nicotine upper head feeling simulation additive and an atomization solvent, wherein the nicotine throat feeling simulation additive is at least one of piperine and 6-methyl nicotine, and the nicotine upper head feeling simulation additive is at least one of cytisine, magnolol and 6-methyl nicotine. The nicotine upper-feeling simulation additive (at least one of cytisine, magnolol and 6-methyl nicotine) can enable brain to generate an upper-feeling effect similar to nicotine, can partially replace the activation effect of nicotine, can bring pain, stimulation, itching and the like to human throat, and forms a throat feeling sensation, wherein the 6-methyl nicotine has a certain effect similar to the upper-feeling effect and the throat feeling effect, so that the nicotine substitution liquid preparation formed by compounding the specific nicotine upper-feeling simulation additive and the nicotine upper-feeling simulation additive with an atomization solvent under a specific proportion can simulate the upper-feeling and the throat feeling brought by nicotine in a synergistic way, the upper-feeling and the throat feeling of the zero-nicotine atomization preparation are improved, the satisfaction feeling generated by a user is improved, the purpose of physiological de-addiction is achieved, and simultaneously the toxicity and the addiction are far lower than the nicotine, and the health damage can be reduced.
Detailed Description
The following examples are provided for a better understanding of the present invention and are not limited to the preferred embodiments described herein, but are not intended to limit the scope of the invention, any product which is the same or similar to the present invention, whether in light of the present teachings or in combination with other prior art features, falls within the scope of the present invention.
The specific experimental procedures or conditions are not noted in the examples and may be followed by the operations or conditions of conventional experimental procedures described in the literature in this field. The reagents or apparatus used were conventional reagent products commercially available without the manufacturer's knowledge.
The core component in the nicotine liquid preparation is nicotine, when the atomizer is heated by a power supply, the nicotine in the nicotine liquid preparation is atomized into aerosol and then inhaled by a human body, wherein one part of aerosol is transmitted to the throat, throat-hitting sensation is caused by stimulating the throat, the other part of aerosol can enter the lung to participate in pulmonary vein circulation and then enter arterial circulation, the nicotine is rapidly transmitted to the brain, and is combined with acetylcholine receptors in the brain to promote the brain to release neurotransmitter (dopamine), and the dopamine release is a pleasant experience, so that the rewarding function of the brain is enhanced, the upper head sensation is generated, the smoker can feel satisfied, but the nicotine has greater toxicity and addiction, and long-term inhalation can influence the health of the human body. The satisfaction is a comprehensive evaluation of the upper head feeling and the throat feeling, and the proper throat feeling contributes to the improvement of the comprehensive satisfaction, but if the throat feeling is too strong, the suction stimulation is too high, the physiological discomfort is caused, and the satisfaction is reduced. At present, in order to prevent abuse of nicotine and ensure public health and safety, strict supervision of nicotine of electronic cigarette products by various countries promotes the problem that zero nicotine products avoid nicotine addiction in many countries. The zero-nicotine atomized preparation product mainly has rich taste and cool feeling, but the existing zero-nicotine atomized preparation does not have throat-hitting feeling and head-up feeling caused by nicotine because of no nicotine, and the product has weak satisfaction and can not lead consumers to be addicted physiologically.
Cytisine is a natural bioactive compound, and is mainly separated from leguminous plants (especially seeds of honeysuckle flowers) and used as an auxiliary tool for clinical management of smoking cessation. The main target of the action of cytisine is neuronal nicotinic acetylcholine receptors (nAChRs) to which it binds capable of producing neurotransmitters such as dopamine, which act similarly to nicotine.
Magnolol belongs to a main active ingredient in a magnolia bark extract, and magnolia bark belongs to a traditional Chinese medicine and has various pharmacological activities. In recent years, research on magnolol at home and abroad is continued, and studies show that magnolol has wide pharmacological effects, such as antidepressant, monoamine transmitter regulation, anti-inflammatory, nerve protection and the like, and the magnolol can improve the 5-hydroxytryptamine and dopamine levels of the frontal cortex of the mouse.
6-Methyl nicotine (CAS: 13270-56-9) is a synthetic organic substance, which is a nicotine analog, with a very similar throat feel as nicotine, and the inventors found that the throat feel of 6-methyl nicotine is very evident in the subjective pumping experience. Nicotine substitutes have affinity for nicotinic acetylcholine receptors (nAChR) associated with the lipophilicity of the 6-substituent. Related studies have further shown that as the size of the substituents increases, the affinity decreases. The affinity of the nicotine analog is determined by the lipophilicity of the substituent at position 6 and is also dependent on the size of the substituent. Among them, 6-methyl nicotine has the least 6-substituted area, has strong lipophilicity and strong affinity with nAChR receptors, and thus, 6-methyl nicotine can produce a feeling of upper head similar to nicotine.
Piperine is an alkaloid, is a source of peppery taste of peppers, and is also the most important bioactive ingredient. Piperine is a regulator of human Transient Receptor Potential (TRP) channel, and after the piperine has the effect of activating the TRP channel, throat feeling such as pain, stimulation, itching and the like can be brought to people, so that throat feeling similar to nicotine is formed. In addition, it is scientifically found that piperine can inhibit enzymes of other substances with important roles in the drug metabolism process, and the piperine can improve the bioavailability of a plurality of compounds by inhibiting the drug metabolism process, so that the bioactivity of other alkaloids on human bodies is improved, and the upper head feeling is assisted to be improved.
The inventor unexpectedly finds that piperine and 6-methyl nicotine are used as nicotine throat-hitting sense simulation additives, cytisine, magnolol and 6-methyl nicotine are used as nicotine head-hitting sense simulation additives, and the throat-hitting sense and head-hitting sense brought by the nicotine are matched and simulated in a synergistic manner through different groups between the nicotine throat-hitting sense simulation additives and the nicotine head-hitting sense simulation additives, so that the throat-hitting sense and head-hitting sense of zero-nicotine products are improved, and high satisfaction is generated.
The invention provides a nicotine replacement liquid preparation, which comprises a nicotine throat feel simulation additive, a nicotine upper head feel simulation additive and an atomization solvent, wherein the nicotine throat feel simulation additive is at least one of piperine and 6-methyl nicotine, and the nicotine upper head feel simulation additive is at least one of cytisine, magnolol and 6-methyl nicotine. The inventor finds that the nicotine upper feeling simulation additive (at least one of cytisine, magnolol and 6-methyl nicotine) can cause the brain to generate an upper feeling effect similar to nicotine, can partially replace the activation effect of the nicotine, can bring pain, stimulation, itching and the like to the throat of a human body, and forms a throat feeling, and the 6-methyl nicotine simultaneously has a certain upper feeling effect and throat feeling effect similar to the nicotine, so that the nicotine formed by compounding the specific nicotine upper feeling simulation additive and the nicotine upper feeling simulation additive with an atomization solvent in a specific proportion replaces a liquid preparation, and cooperates with the upper feeling and throat feeling brought by the simulated nicotine, so that the upper feeling and throat feeling of the zero nicotine atomization preparation are improved, the satisfaction feeling generated by a user is improved, the aim of physiological de-addiction is fulfilled, and simultaneously the toxicity and addiction are far lower than the nicotine, and the health damage can be reduced.
In some alternative embodiments, the nicotine replacement liquid formulation has a total mass content of nicotine throat feel simulating additive and nicotine top head feel simulating additive of 2.1-61mg/g. For example, the nicotine-substituted liquid preparation comprises the following nicotine-throat sensation-simulating additive and nicotine-upper-head sensation-simulating additive in total mass content 2.1mg/g、2.5mg/g、2.6mg/g、3mg/g、3.5mg/g、4mg/g、4.5mg/g、5mg/g、5.6mg/g、6mg/g、7mg/g、8mg/g、9mg/g、10mg/g、11mg/g、12mg/g、13mg/g、14mg/g、15mg/g、16mg/g、17mg/g、18mg/g、19mg/g、20mg/g、22mg/g、23mg/g、24mg/g、25mg/g、26mg/g、27mg/g、28mg/g、29mg/g、30mg/g、31mg/g、32mg/g、33mg/g、34mg/g、35mg/g、36mg/g、37mg/g、38mg/g、39mg/g、40mg/g、41mg/g、42mg/g、43mg/g、44mg/g、45mg/g、46mg/g、47mg/g、48mg/g、49mg/g、50mg/g、51mg/g、52mg/g、53mg/g、54mg/g、55mg/g、56mg/g、57mg/g、58mg/g、59mg/g、60mg/g、61mg/g.
In some alternative embodiments, the mass ratio of the nicotine throat-feel simulation additive to the nicotine top-feel simulation additive is (0.1-11): 2-50. For example, alternatively, the inventors found that by controlling the mass ratio of the nicotine throat-feel simulation additive to the nicotine top-feel simulation additive to be in the range of (0.1-11): 2-50, the satisfaction of the user is improved, and even better than the satisfaction of the market with benzoic acid as the organic acid, with a nicotine content of 10 mg/g.
The raw material components of the nicotine replacement liquid preparation comprise 6-methyl nicotine and an atomization solvent. The inventor finds that the 6-methyl nicotine has the effect of similar upper head feeling and throat feeling of the nicotine, can well improve the satisfaction of users, is even better than the nicotine, has toxicity and addiction far lower than the nicotine, and can reduce the damage to human health.
In some alternative embodiments, the mass ratio of 6-methyl nicotine to nebulized solvent is from (0.3 to 5): from (40 to 95). For example, the mass ratio of 6-methyl nicotine to the atomizing solvent can be selected to be 0.3：40、0.3：45、0.3：47、0.3：50、0.3：51、0.3：55、0.3：60、0.3：65、0.3：70、0.3：74、0.3：80、0.3：85、0.3：90、0.3：95、0.5：40、0.5：45、47、0.5：50、0.5：51、0.5：55、0.5：60、0.5：65、0.5：70、0.5：74、0.5：80、0.5：85、0.5：90、0.5：95、1：40、1：45、1：47、1：50、1：51、1：55、1：60、1：65、1：70、1：74、1：80、1：85、1：90、1：95、1.5：40、1.5：45、1.5：47、1.5：50、1.5：51、1.5：55、1.5：60、1.5：65、1.5：70、1.5：74、1.5：80、1.5：85、1.5：90、1.5：95、2：40、2：45、2：47、2：50、2：51、2：55、2：60、2：65、2：70、2：74、2：80、2：85、2：90、2：95、3：40、3：45、3：47、3：50、3：51、3：55、3：60、3：65、3：70、3：74、3：80、3：85、3：90、3：95、4：40、4：45、4：47、4：50、4：51、4：55、4：60、4：65、4：70、4：74、4：80、4：85、4：90、4：95、5：40、5：45、5：47、5：50、5：51、5：55、5：60、5：65、5：70、5：74、5：80、5：85、5：90、5：95.
In some alternative embodiments, the raw material components of the nicotine replacement liquid formulation include a nicotine throat feel simulating additive, a nicotine top feel simulating additive and an atomizing solvent, wherein the nicotine throat feel simulating additive is selected from at least one of piperine and 6-methyl nicotine, and the nicotine top feel simulating additive is selected from at least one of cytisine and magnolol.
In some alternative embodiments, the nicotine throat feel simulating additive is piperine, the nicotine upper head feel simulating additive is cytisine, in some alternative embodiments, the nicotine throat feel simulating additive is piperine, the nicotine upper head feel simulating additive is magnolol, in other alternative embodiments, the nicotine throat feel simulating additive is piperine, the nicotine upper head feel simulating additive is cytisine and magnolol, the mass ratio of the cytisine to the magnolol is (5-40), for example, the mass ratio of the cytisine to the magnolol is 5：5、5：6、5：8、10、5：11、5：13、5：15、5：17、5：19、5：20、5：21、5：23、5：25、5：26、5：28、5：29、5：30、7：5、7：6、7：8、10、7：11、7：13、7：15、7：17、7：19、7：20、7：21、7：23、7：25、7：26、7：28、7：29、7：30、10：5、10：6、10：8、10、10：11、10：13、10：15、10：17、10：19、10：20、10：21、10：23、10：25、10：26、10：28、10：29、10：30、15：5、15：6、15：8、10、15：11、15：13、15：15、15：17、15：19、15：20、15：21、15：23、15：25、15：26、15：28、15：29、15：30、20：5、20：6、20：8、10、20：11、20：13、20：15、20：17、20：19、20：20、20：21、20：23、20：25、20：26、20：28、20：29、20：30、25：5、25：6、25：8、10、25：11、25：13、25：15、25：17、25：19、25：20、25：21、25：23、25：25、25：26、25：28、25：29、25：30、30：5、30：6、30：8、10、30：11、30：13、30：15、30：17、30：19、30：20、30：21、30：23、30：25、30：26、30：28、30：29、30：30、35：5、35：6、35：8、10、35：11、35：13、35：15、35：17、35：19、35：20、35：21、35：23、35：25、35：26、35：28、35：29、35：30、40：5、40：6、40：8、10、40：11、40：13、40：15、40：17、40：19、40：20、40：21、40：23、40：25、40：26、40：28、40：29、40：30., the cytisine and the magnolol can be selected, the compound is carried out through the piperine, the cytisine and the magnolol, and the satisfaction improvement on the user is obviously higher than the compound of the cytisine and the piperine or the compound of the magnolol and the piperine singly.
In some alternative embodiments, the nicotine throat feel mimetic additive is 6-methyl nicotine, the nicotine upper-taste mimetic additive is cytisine, in some alternative embodiments, the nicotine throat feel mimetic additive is 6-methyl nicotine, the nicotine upper-taste mimetic additive is magnolol, in other alternative embodiments, the nicotine throat feel mimetic additive is 6-methyl nicotine, the nicotine upper-taste mimetic additive is cytisine and magnolol, the mass ratio of the cytisine and the magnolol is (1-25): 1-5, for example, the mass ratio of the cytisine and the magnolol is 1：1、2：1、5：1、7：1、9：1、10：1、12：1、13：1、15：1、18：1、19：1、20：1、21：1、24：1、25：1、1：2、2：2、5：2、7：2、9：2、10：2、12：2、13：2、15：2、18：2、19：2、20：2、21：2、24：2、25：2、1：3、2：3、5：3、7：3、9：3、10：3、12：3、13：3、15：3、18：3、19：3、20：3、21：3、24：3、25：3、1：4、2：4、5：4、7：4、9：4、10：4、12：4、13：4、15：4、18：4、19：4、20：4、21：4、24：4、25：4、1：5、2：5、5：5、7：5、9：5、10：5、12：5、13：5、15：5、18：5、19：5、20：5、21：5、24：5、25：5., the compound is 6-methyl nicotine, the cytisine and the magnolol, and the satisfaction of a user is obviously improved compared with the compound of the cytisine and the 6-methyl nicotine or the compound of the magnolol and the 6-methyl compound of the single use.
In some alternative embodiments, the nebulized solvent may be at least one of the conventional nebulized solvents known in the art, including but not limited to propylene glycol, glycerin, and optionally the ratio of the total mass of the nicotine throat feel simulating additive and the nicotine top head feel simulating additive to the nebulized solvent is (0.3-5): (40-95), e.g., alternatively the ratio of the total mass of the nicotine throat feel simulating additive and the nicotine top head feel simulating additive to the nebulized solvent is 0.3：40、0.3：45、0.3：47、0.3：50、0.3：51、0.3：55、0.3：60、0.3：65、0.3：70、0.3：74、0.3：80、0.3：85、0.3：90、0.3：95、0.5：40、0.5：45、47、0.5：50、0.5：51、0.5：55、0.5：60、0.5：65、0.5：70、0.5：74、0.5：80、0.5：85、0.5：90、0.5：95、1：40、1：45、1：47、1：50、1：51、1：55、1：60、1：65、1：70、1：74、1：80、1：85、1：90、1：95、1.5：40、1.5：45、1.5：47、1.5：50、1.5：51、1.5：55、1.5：60、1.5：65、1.5：70、1.5：74、1.5：80、1.5：85、1.5：90、1.5：95、2：40、2：45、2：47、2：50、2：51、2：55、2：60、2：65、2：70、2：74、2：80、2：85、2：90、2：95、3：40、3：45、3：47、3：50、3：51、3：55、3：60、3：65、3：70、3：74、3：80、3：85、3：90、3：95、4：40、4：45、4：47、4：50、4：51、4：55、4：60、4：65、4：70、4：74、4：80、4：85、4：90、4：95、5：40、5：45、5：47、5：50、5：51、5：55、5：60、5：65、5：70、5：74、5：80、5：85、5：90、5：95., and the nebulized solvent is propylene glycol and glycerin. The mass ratio of the propylene glycol to the glycerol is (1-50), and optionally (1-50), and the mass ratio of the propylene glycol to the glycerol ethanol is 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、2：10、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 atomization solvent can better dissolve raw material components, effectively improve the atomization efficiency of nicotine and increase the satisfaction.
In some alternative embodiments, the nicotine replacement liquid formulation has a mass content of the nicotine throat feel simulating additive of 0.1-11mg/g and a mass content of the nicotine head feel simulating additive of 2-50mg/g. For example, the nicotine replacement liquid formulation may optionally have a mass content of A of 0.1mg/g、0.5mg/g、0.7mg/g、0.9mg/g、1mg/g、1.1mg/g、1.5mg/g、1.7mg/g、2mg/g、2.3mg/g、2.5mg/g、2.7mg/g、3mg/g、3.5mg/g、3.7mg/g、4mg/g、4.5mg/g、4.8mg/g、5mg/g、5.5mg/g、5.8mg/g、6mg/g、6.5mg/g、5.7mg/g、7mg/g、7.5mg/g、7.7mg/g、8mg/g、8.5mg/g、9mg/g、9.5mg/g、10mg/g、10.5mg/g、11mg/g, and a mass content of the sensory cue additive on nicotine of 2mg/g、3mg/g、4mg/g、5mg/g、6mg/g、7mg/g、8mg/g、9mg/g、10mg/g、11mg/g、12mg/g、13mg/g、14mg/g、15mg/g、16mg/g、17mg/g、18mg/g、19mg/g、20mg/g、21mg/g、22mg/g、23mg/g、24mg/g、25mg/g、26mg/g、27mg/g、28mg/g、29mg/g、30mg/g、31mg/g、32mg/g、33mg/g、34mg/g、35mg/g、36mg/g、37mg/g、38mg/g、39mg/g、40mg/g、41mg/g、42mg/g、43mg/g、44mg/g、45mg/g、46mg/g、47mg/g、48mg/g、49mg/g、50mg/g.
In some alternative embodiments, the raw material component of the nicotine replacement liquid formulation further comprises an organic acid. Optionally, the organic acid comprises at least one of C3-C8 organic carboxylic acid, and further optionally, the organic acid comprises at least one of C3-C8 mono-organic carboxylic acid, C3-C8 di-organic carboxylic acid, and C3-C8 tri-organic carboxylic acid. Still further optionally, the organic acid comprises at least one of salicylic acid, citric acid, malic acid, benzoic acid, levulinic acid, tartaric acid, and succinic acid, and still further optionally, the organic acid is benzoic acid. The invention can further ensure the satisfaction of users by further adding specific organic acid into the raw material components to form the nicotine salt.
In some alternative embodiments, the molar amount of organic acid to the molar amount of 6-methyl nicotine is 1 (0.98-1.5) on a carboxyl basis, for example, alternatively the molar amount of organic acid to the molar amount of 6-methyl nicotine is 1:0.98, 1:0.99, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 on a carboxyl basis. After adding 6-methyl nicotine in the nicotine top-up feeling simulation additive and/or the nicotine throat-hitting feeling simulation additive, the inventors further found that the organic acid and the addition amount thereof affect the satisfaction. Changing the molar ratio of the organic acid and the 6-methyl nicotine can change the acid-base environment of the throat, and adjust the throat feeling in the lung entering process of aerosol. Preferably, the molar amount of the organic acid to the molar amount of 6-methylnicotine is 1:1, calculated as carboxyl groups.
In some alternative embodiments, the raw material component of the nicotine replacement liquid formulation further comprises a flavor. The essence can be conventional existing essence materials in the field, can be obtained commercially or prepared by conventional methods through conventional components, and can be prepared by preparing monomer perfume raw materials or various extracts. Including but not limited to tobacco flavor, fruit flavor, and mint flavor. Further, the fruit essence comprises at least one of mango essence, blueberry essence and grape essence, optionally, the ratio of the total mass of the nicotine throat-sensation simulation additive and the nicotine top-sensation simulation additive to the essence is (0.3-5): 20-45, for example, optionally, the ratio of the total mass of the nicotine throat-sensation simulation additive and the nicotine top-sensation simulation additive to the essence is 0.3：20、0.3：25、0.3：30、0.3：35、0.3：40、0.3：45、0.5：20、0.5：25、0.5：30、0.5：35、0.5：40、0.5：45、1：20、1：25、1：30、1：35、1：40、1：45、1.5：20、1.5：25、1.5：30、1.5：35、1.5：40、1.5：45、2：20、2：25、2：30、2：35、2：40、2：45、3：20、3：25、3：30、3：35、3：40、3：45、4：20、4：25、4：30、4：35、4：40、4：45、5：20、5：25、5：30、5：35、5：40、5：45.
The invention also provides a preparation method of the nicotine replacement liquid preparation, which comprises the following steps of mixing the nicotine throat feeling simulation additive, the nicotine upper head feeling simulation additive and the atomized solvent, and heating and stirring uniformly.
In some alternative embodiments, the method of making the nicotine replacement liquid formulation further comprises the step of adding a flavor.
In some alternative embodiments, the method of making the nicotine replacement liquid formulation further comprises the step of adding an organic acid.
The invention does not limit the heating and stirring temperature and time, as long as the raw materials can be dissolved, and the dissolution temperature is not higher than 100 ℃ optionally. Optionally, the heating and stirring temperature is 40-65 ℃ and the heating and stirring time is 20-30min. The invention does not need to specifically advance the mixing mode and the mixing sequence, and can be used for heating and dissolving all the raw materials after being mixed, or mixing and dissolving part of the raw materials, and then mixing and dissolving the rest of the raw materials.
In some alternative embodiments, the preparation method of the nicotine replacement liquid preparation comprises the following steps of mixing the nicotine upper head feeling simulation additive, the nicotine throat feeling simulation additive, the organic acid and part of atomized solvent, heating at 40-65 ℃ for 20-30 minutes to dissolve and mix uniformly, cooling to 10-35 ℃, adding essence, and stirring for 5-40 minutes to mix uniformly, thus obtaining the nicotine replacement liquid preparation.
In some alternative embodiments, the preparation method of the nicotine replacement liquid preparation comprises the following steps of mixing the nicotine upper head feeling simulation additive, the nicotine throat feeling simulation additive, the organic acid and part of atomized solvent, heating at 40-65 ℃ for 20-30 minutes to dissolve and mix uniformly, cooling to room temperature, adding essence, and stirring for 5-40 minutes to mix uniformly, thus obtaining the nicotine replacement liquid preparation.
The invention also provides an application of the nicotine replacement liquid preparation or the nicotine replacement liquid preparation prepared by the preparation method in an atomization device. Optionally, the atomization device is an electronic atomization device.
Example 1
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.6g of 6-methyl nicotine, 1g of magnolol, 0.42g of benzoic acid, 12.98g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Example 2
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.6g of 6-methyl nicotine, 1g of cytisine, 0.42g of benzoic acid, 12.98g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Example 3
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.01g of piperine, 4.5g of cytisine, 10.49g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, and stirring for 20min to uniformly mix to obtain the nicotine replacement liquid preparation.
Example 4
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.01g of piperine, 4.5g of magnolol, 10.49g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, and stirring for 20min to uniformly mix to obtain the nicotine replacement liquid preparation.
Example 5
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
3g of cytisine, 1.5g of magnolol, 0.01g of piperine, 10.49g of propylene glycol and 40g of glycerol are mixed, stirred at 60 ℃ for 20min to uniformly mix, cooled to room temperature, and then 45g of blueberry essence is added to uniformly mix for 20min to obtain the nicotine replacement liquid preparation.
Example 6
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
3.0g of cytisine, 1.5g of magnolol, 0.05g of piperine, 10.45g of propylene glycol and 40g of glycerol are mixed, stirred at 60 ℃ for 20min to uniformly mix, cooled to room temperature, and then 45g of blueberry essence is added to uniformly mix, so that the nicotine replacement liquid preparation is obtained.
Example 7
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
3.0g of cytisine, 1.5g of magnolol, 0.1g of piperine, 10.4g of propylene glycol and 40g of glycerol are mixed, stirred at 60 ℃ for 20min to uniformly mix, cooled to room temperature, and then 45g of blueberry essence is added to uniformly mix for 20min to obtain the nicotine replacement liquid preparation.
Example 8
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.3g of 6-methyl nicotine, 0.21g of benzoic acid, 14.49g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Example 9
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.6g of 6-methyl nicotine, 0.42g of benzoic acid, 13.98g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, and stirring for 20min to uniformly mix to obtain the nicotine replacement liquid preparation.
Example 10
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
mixing 1.0g of 6-methyl nicotine, 0.69g of benzoic acid, 13.31g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, and stirring for 20min to uniformly mix to obtain the nicotine replacement liquid preparation.
Example 11
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.6g of 6-methyl nicotine, 0.5g of cytisine, 0.5g of magnolol, 0.42g of benzoic acid, 12.98g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Example 12
The embodiment provides a preparation method of a nicotine replacement liquid preparation, comprising the following steps:
Mixing 0.6g of 6-methyl nicotine, 3.0g of cytisine, 1.5g of magnolol, 0.42g of benzoic acid, 9.48g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Example 13
Mixing 1.0g of 6-methyl nicotine, 3.0g of cytisine, 1.5g of magnolol, 0.69g of benzoic acid, 8.81g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Comparative example 1
The comparative example provides a method for preparing a nicotine replacement liquid preparation, comprising the following steps:
Mixing 15g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Comparative example 2
The comparative example provides a method for preparing a nicotine liquid preparation, comprising the following steps:
mixing 1g of nicotine, 0.75g of benzoic acid, 13.25g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine liquid preparation.
Comparative example 3
The comparative example provides a method for preparing a nicotine liquid preparation, comprising the following steps:
Mixing 2g of nicotine, 1.5g of benzoic acid, 11.5g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine liquid preparation.
Comparative example 4
The comparative example provides a method for preparing a nicotine liquid preparation, comprising the following steps:
Mixing 3g of nicotine, 2.26g of benzoic acid, 9.74g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine liquid preparation.
Comparative example 5
The comparative example provides a method for preparing a nicotine replacement liquid preparation, comprising the following steps:
Mixing 3.0g of cytisine, 12g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, and stirring for 20min to uniformly mix to obtain the nicotine replacement liquid preparation.
Comparative example 6
The comparative example provides a method for preparing a nicotine replacement liquid preparation, comprising the following steps:
Mixing 1.5g of magnolol, 13.5g of propylene glycol and 40g of glycerol, stirring at 60 ℃ for 20min to uniformly mix, cooling to room temperature, adding 45g of blueberry essence, stirring for 20min to uniformly mix, and obtaining the nicotine replacement liquid preparation.
Test case
The present invention scores each of the liquid formulations of examples 1 to 13 and comparative examples 1 to 6 for the absorption index by the subjective absorption method. 15 persons in the smoking team all have more than 3 years of experience with traditional cigarette or e-cigarette smoking and nicotine withdrawal is performed 10 hours before smoking.
And (3) taking a sample of each person by taking a sample of the evaluation list, and taking nicotine replacement liquid preparation or nicotine liquid preparation of different examples and comparative examples by adopting a dark evaluation mode, wherein the sample taking method comprises the steps of taking nicotine withdrawal for 10 hours in the evening before taking the sample, taking a sample of the test at 9 am on the day, taking 10 mouths of flue gas (3 s for each mouths of the flue gas and 27s for each mouths of the flue gas) together by using RELX generation electronic cigarette rods (matched with different examples and comparative examples), and taking scoring evaluation according to the evaluation indexes in the table 1 after taking the flue gas. After the sample smoke oil is completely sucked, the sample smoke oil is stopped for 2 hours, and then the sample smoke oil is subjected to the sample suction test. The results of the wicking test are shown in Table 2 (scoring values are average scores).
Table 1 evaluation index
Table 2 product suction scoring data
The liquid formulations (hereinafter abbreviated as samples) prepared in example 1, example 2, example 11 and comparative example 1 were subjected to a aspiration process heart rate test. The test method comprises the steps that a person taking the product performs nicotine withdrawal in the evening before the test of taking the product, and the heart rate test of the product taking process is performed on the day 9 am. Before the product is sucked, the heart rate testing instrument is worn (the heart rate testing instrument is Lepu heart and an treasured ER 1), and the whole product sucking process monitors the real-time change of the heart rate. After the heart rate instrument is worn and debugged, a standard heart rate test is carried out for 2 minutes. After the heart rate is stable, heart rate monitoring of the smoking process is started, RELX smoke rods (matched with samples of different embodiments and comparative examples) are used for sucking 5 smoke (each smoke is sucked for 3s, and the interval between two adjacent smoke is 27 s), the whole smoking time is about 2.5min, and the time of starting to suck each smoke is recorded. After the aspiration, the heart rate change was monitored for another 1min, and the experiment was ended. After one sample was completed, the heart rate test was performed for the next sample withdrawal process after 2 hours of withdrawal. The test results are shown in fig. 1 and 2, wherein the average normalized heart rate of fig. 1 is the ratio of the average monitored heart rate during the aspiration to the average reference heart rate, and the normalized heart rate of fig. 2 is the ratio of the real-time monitored heart rate during the aspiration to the average reference heart rate over the 2 minutes.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.