CN113208148B - A supramolecular gel for synergistic release of nicotine and aroma components - Google Patents

Abstract

The invention belongs to the field of supramolecular gel, and particularly relates to supramolecular gel for synergistically releasing nicotine and aroma components. The gel comprises a racemic nicotine mandelate gelling agent and a flavor substance and a solvent dispersed in the racemic nicotine mandelate gelling agent. The invention uses a gel medium to associate the originally separated nicotine salt system and the flavor system to form a new substance form (gel) and to associate the originally separated physiological satisfaction and relaxation to the characteristic taste of the mouth-eating taste to form a new comprehensive sensory perception (resulting from the synergistic release of nicotine and flavor substances). Through the recombination of the substance level and the sensory level, the nicotine and the aroma components are released synergistically, so that the synergistic sensory experience is obtained.

Description

A supramolecular gel for the synergistic release of nicotine and aromatizing components

technical field

The invention belongs to the field of supramolecular gels, in particular to a supramolecular gel for synergistically releasing nicotine and aroma components.

Background technique

Basic nicotine can react with carboxyl groups of organic acids to form nicotine carboxylate. Nicotine contains a pyridine ring and a pyrrole ring. Among them, the pyrrole ring nitrogen is more basic and tends to react with the carboxyl group of a carboxylic acid to form nicotine salts, while the pyridine ring nitrogen is weaker in basicity and cannot ionize basically. Binds to carboxylic acids through non-covalent interactions such as hydrogen bonds. Tobacco leaves naturally contain various carboxylic acid nicotine salts. According to the acid-base ratio of nicotine salts, nicotine salts can be divided into 1:1 acid-base ratio, 2:1 acid-base ratio, and 3:1 acid-base ratio nicotine salt. Among them, common nicotine carboxylates include nicotine tartrate, nicotine mandelic acid, nicotine malate, nicotine oxalate, nicotine benzoate and the like.

Studies have shown that two complex chemical reactions occur when nicotine salts release nicotine: the first reaction includes dissociation and/or dehydration and decomposition of carboxylic acid anions; the second reaction includes proton transfer between different nicotine forms, single protonation The salt undergoes a disproportionation reaction into a mixture of diprotic salt and free nicotine, and the free nicotine evaporates to achieve a disproportionation equilibrium. Experiments have confirmed that most nicotine salts can release nicotine in two different temperature ranges (110-125°C and 160-210°C). Among them, the nicotine in the low-temperature section comes from the unprotonated nicotine formed by the disproportionation reaction of nicotine salt, and the high-temperature section The nicotine comes from the aprotonated nicotine obtained by the further decomposition/dissociation of the diprotonated nicotine in the above-mentioned disproportionation products. Specifically, there are three ranges of temperature for various nicotine salts to release nicotine when heated: around 115°C (non-protonated nicotine (free nicotine) evaporates/volatilizes), around 165°C (disproportionation of monoprotonated nicotine salts), and 200°C Left and right (diprotonated nicotine salt breakdown/dissociation).

Synthetic nicotine salts can be directly added to electronic cigarettes or heated cigarettes to supplement the amount of nicotine and obtain an effect similar to that of smoking and smoking cigarettes. If the heating temperature of the tobacco leaves exceeds 250°C, the nicotine content in the smoke is similar to that in the smoke of burning and smoking cigarettes. At the same time, when the heating temperature of tobacco leaves does not exceed 350 ° C, the "hazardous and potentially harmful components (HPHCs)" produced and inhaled are significantly reduced compared with burning and smoking cigarettes. Importantly, the transfer rates of nicotine from unprotonated (free) nicotine and carboxylated nicotine salts to the gas phase are comparable in the 250-300°C range. Heated cigarettes avoid the high temperatures of tobacco combustion, and they deliver similar levels of nicotine as smoked cigarettes, but with lower average levels of harmful components.

Current main problems and deficiencies of heated cigarettes:

Heated cigarettes are different from burning and smoking cigarettes in that it takes a long time to preheat the heated cigarette to the working temperature (such as 300°C), which makes the tobacco segment exposed to the range from 125-250°C for a long time, while the nicotine salt is completely Nicotine can be transferred to the gas phase in this temperature range. On the one hand, during the preheating stage, a large amount of volatile flavor components evaporate into the gas phase and escape out of the cigarette with the transfer of nicotine, causing serious aroma attenuation in the middle and later stages of smoking; on the other hand On the one hand, tobacco itself contains a large amount of polycarboxylic acid nicotine salts (such as malic acid and racemic mandelic acid nicotine salt). Decarboxylation occurs and eliminates the reaction to form weakly acidic products such as monocarboxylic acid (such as acetic acid). Due to the slow accumulation of moisture and acidity in the process, problems such as small amount of smoke in the early stage of suction, smoke burning the mouth, and obvious sour feeling are caused.

While maintaining the active ingredients of natural tobacco leaves, reconstituted tobacco leaves have the characteristics of strong plasticity, homogenization and high level of controllability, so it is one of the main tobacco section materials of heated cigarettes at present. The tobacco segments of mainstream heated cigarettes are mostly manufactured by papermaking and thick pulp methods. Due to the influence of the coating rate, the papermaking process has a slightly lower smoke and aroma, and the high content (12%-20%) of the smoke agent is mainly coated on the surface of the reconstituted tobacco leaf, which is easy to leach and absorb moisture. In order to improve the aroma of reconstituted tobacco leaves, refined processing such as solvent extraction of tobacco leaves and molecular distillation are usually used to prepare tobacco extracts with high aroma and high nicotine content and add them to the coating liquid. The process is cumbersome and complicated, and the manufacturing cost is relatively high; In order to meet the load function of the base, it is necessary to develop a relatively complex special base; the surface viscosity of reconstituted tobacco leaves is high and the elasticity is poor, which increases the difficulty of the subsequent shredding process. Thick pulp reconstituted tobacco leaves have a relatively high slurry moisture (about 80%) during molding, and need to remove relatively high moisture during drying, which is likely to cause the loss of aroma components and smoke-generating agents. To sum up, the reconstituted tobacco leaves for cigarettes heated by the papermaking method and the thick pulp method currently mainly have problems such as low aroma and smoke production, and high smoke-generating agents such as leaching from the tobacco section and moisture absorption, which directly affect product quality and smoking sense. quality.

The current main problems and defects of electronic cigarette liquid:

The nicotine used in e-cigarette liquid was originally called "free base" nicotine. Free base nicotine is volatile. As a result, when consumers inhale e-cigarette aerosols, nicotine is likely to be released as a gas from the aerosol particles, deposited in the mouth/upper respiratory tract, and absorbed by the blood. The absorption in the oral cavity/upper respiratory tract is slower than that of traditional cigarettes, and pharmacokinetic studies have shown that it is closer to nicotine replacement therapy (NRT) products than traditional cigarettes. To this end, e-liquids containing nicotine salts have been introduced. Nicotine salts are less volatile than free base nicotine. Pharmacokinetic studies have shown that nicotine carboxylate can deliver nicotine through the lungs, increasing the rate of absorption without exceeding the maximum nicotine concentration of traditional cigarettes, while having acceptable subjective satisfaction and ease required for smoking. At present, the representative nicotine salt in commercially available electronic cigarettes is nicotine benzoate.

Although nicotine salts have been widely used in e-cigarette liquids, there are still the following main sensory problems in e-cigarettes containing nicotine salts: when nicotine salts are heated and decomposed to form free nicotine and delivered to the atomized vapor, puff-by-puff nicotine The release behavior is inconsistent with the release behavior of the aromatizing ingredients, and it is difficult to achieve the synergistic delivery of the key aromatizing ingredients and nicotine. While bringing nicotine physiological satisfaction, it cannot bring the matching characteristic fragrance, resulting in the interaction between nicotine and flavoring substances. The sensory sensations are strong and weak, covering each other or even repelling each other, especially for volatile characteristic aroma substances, because they cannot be released stably throughout the smoking process (usually the release amount gradually decreases mouth by mouth), this sense of incongruity Especially obvious. The reason may be that: from the material level, the nicotine salt and flavors and fragrances in the e-liquid belong to different systems. The former belongs to the nicotine release system, and the latter belongs to the flavor substance release system. The two can be connected as a whole medium, and each has its own atomization behavior at the same atomization temperature; from the sensory perspective, nicotine salt mainly provides appropriate physiological satisfaction and relaxation, and flavors and fragrances mainly provide characteristics through evaporation The suction and taste of the taste, because the atomization behavior of the two is different when smoking, the sensory characteristics are also separated. Another common problem with e-cigarettes is that during the storage of e-liquid or pods, it is inevitable that there will be a problem of volatilization and loss of flavor components. Even in closed pods, there will be a problem of deterioration of flavor substances. At present, although microcapsule technology can be used to encapsulate volatile aroma components, since microcapsules mostly use sugars such as cyclodextrin as wall materials, there will be a problem caused by the wall material adhering to the heating element at the heating temperature of the electronic cigarette. burning smell and discomfort. The stabilization of aroma substances in e-liquid, especially volatile aroma substances, is still the main problem to be solved in electronic cigarettes.

Contents of the invention

In order to improve the above-mentioned defects of heating cigarettes and electronic cigarettes, the present invention discloses a kind of fragrance-carrying supramolecular gel based on nicotine salt gelling agent for the first time, the fiber network formed by self-assembly of a small amount of nicotine salt gelling agent Matrix, loaded with a large amount of solvent (smoke agent) dissolved with flavoring substances, utilizing the gel's inherent high aroma loading, high solvent (smoke agent) loading, thermally reversible properties, and a supramolecular network different from conventional nicotine salt molecules Structural stability can be applied to the fields of heating cigarettes and electronic cigarettes.

Explanation of terms:

Supramolecular gels: Supramolecular gels are prepared from small molecules ( _Mw < 3000) commonly known as low molecular weight gelling agents (LMWGs). When these compounds are made into supramolecular gels, LMWGs self-assemble through various non-covalent interactions (such as hydrogen bonds, π-π stacking, electrostatic interactions, complexation and hydrophobic interactions, etc.) to form self-assembled fiber networks (SAFINs ) to immobilize solvent molecules. The physical gels obtained from low molecular weight organic gelling agents (LMOGs) are usually thermoreversible (reversible sol-gel transition occurs upon heating and cooling). When the gelling agent containing the solution is cooled, the growth of one-dimensional (1D) fibers can be promoted, which somehow self-assemble into complex three-dimensional (3D) SAFINs, and the solvent molecules are fixed by capillary action to form gels. glue.

The first aspect of the present invention provides a supramolecular gel for the synergistic release of nicotine and aromatizing ingredients, the gel comprising racemic mandelic acid nicotine salt gelling agent and dispersed in the racemic mandelic acid nicotine salt gelling agent Fragrance substances and solvents in the agent;

Wherein, the racemic mandelic acid nicotine salt gelling agent is a three-dimensional network structure formed by self-assembly of one-dimensional fibers, and the one-dimensional fiber structure is formed by multiple racemic mandelic acid and nicotine. Mandelic acid nicotine salt supramolecular structural units are connected, and the connection between the racemic mandelic acid nicotine salt supramolecular structural units is as follows:

The formation principle of the above-mentioned racemic mandelic acid nicotine salt gelling agent is: nicotine and carboxylic acid molecules are combined into supramolecular structural units through synthons, and then the supramolecular structural units are connected by intermolecular forces such as hydrogen bonds It is a one-dimensional fiber structure, and then the one-dimensional fiber structure self-assembles to form a three-dimensional network structure.

Preferably, the fragrance substance is selected from the group consisting of: jasmone, anisone, gingerone, muscone, civetone, nerolidol, farnesol, β-caryophyllenol, β-santalol, α-santalol, Jasmonal, Vanillin, Ethyl Vanillin, Piperonal, Cinnamaldehyde, Methyl Laurate, Ethyl Laurate, Methyl Myristate, Ethyl Myristate, Geranyl Benzoate, Aryl Benzoate One or more of camphor, phenylacetic acid, and β-caryophyllene.

Preferably, the organic solvent is ethyl acetate or a mixed solvent of ethyl acetate and 1,2-propanediol.

The second aspect of the present invention provides a method for preparing a supramolecular gel that synergistically releases nicotine and aromatizing components, comprising the following steps:

Step 1. Preparation of gelling agent: Dissolve racemic mandelic acid and nicotine in a mixed solvent of water and isopropanol in a molar ratio of 2:1, stir at room temperature until completely dissolved, and obtain racemic almonds respectively Acid solution and nicotine solution, and then the above two solutions are fully mixed to obtain a mixed solution, the mixed solution is heated to reflux, reacted for more than 30 minutes, rotary steamed, and then the product obtained by rotary steamed is dried at 30-40 ° C for 20 ~30h, to obtain racemic mandelic acid nicotine salt gelling agent;

Step 2, preparation of gel:

Use an organic solvent to dissolve the flavoring substance to obtain a flavoring substance solvent; then add the flavoring substance solvent to the racemic mandelic acid nicotine salt gelling agent obtained in step 1, dissolve it by heating and stirring or ultrasonic treatment, and then A gel formed on standing in an ice-water bath.

Preferably, when stirring or mixing the above-mentioned solution containing racemic mandelic acid, it is heated to 30-40 degrees Celsius.

The temperature of the ice-water bath is preferably: 0-5 degrees Celsius, such as 0 degrees Celsius, 1 degrees Celsius, 2 degrees Celsius, 3 degrees Celsius, 4 degrees Celsius, 5 degrees Celsius.

Preferably, in step 1, in the mixed solvent of water and isopropanol, the volume content of water is less than 20%; the mass volume ratio of racemic mandelic acid and the mixed solvent of water and isopropanol is 1g:20～30mL, The mass volume ratio of the mixed solvent of nicotine, water and isopropanol is 1g:100-300mL, the rotary steaming temperature is 50-60°C, and the rotary steaming pressure is 120-140mbar.

Because of the high boiling point of the solvent isopropanol, the vacuum degree of rotary evaporation is correspondingly increased.

In step 1, select the mixed solvent of water and isopropanol as solvent, be because racemic mandelic acid can dissolve in isopropanol, add a small amount of water in order to promote carboxylic acid partial ionization, and prevent that adding too much carboxylic acid completely Salt formation reaction occurs after ionization.

Nicotine is soluble in isopropyl alcohol. Isopropanol can also be used alone to dissolve nicotine.

Preferably, in step 2, the mass volume ratio of flavoring substance and organic solvent is 1g:20～30mL, the mass volume ratio of racemic mandelic acid nicotine salt gelling agent and flavoring substance solvent is 1g:20～30mL, ice The temperature of the water bath is 4°C, and the standing time in the ice-water bath is 1-3 hours. Because the required amount of fragrance substance and gelling agent is relatively small, and the amount of solvent is relatively large, it is easier to operate by using mass-volume ratio during actual operation.

Preferably, the fragrance substance is selected from the group consisting of: jasmone, anisone, gingerone, muscone, civetone, nerolidol, farnesol, β-caryophyllenol, β-santalol, α-santalol, Jasmonal, Vanillin, Ethyl Vanillin, Piperonal, Cinnamaldehyde, Methyl Laurate, Ethyl Laurate, Methyl Myristate, Ethyl Myristate, Geranyl Benzoate, Aryl Benzoate One or more of camphor, phenylacetic acid, and β-caryophyllene.

Theoretically, ethanol can also be replaced by methanol or acetone, but methanol is more toxic and acetone is too volatile, so it is generally not used.

Since the formation of the racemic mandelic acid nicotine salt gelling agent is driven by the synergistic effect of hydrogen bonds and π-π stacking, the overall performance is medium polarity, so the fragrance material of the present invention is selected from medium polar substances, and the organic solvent is selected Ethyl acetate-1,2-propanediol mixed solvent.

The aroma substances of the present invention are medium polar substances and belong to semi-volatile aroma substances. Standing in an ice-water bath can maintain the stability of semi-volatile aroma substances.

Preferably, the organic solvent is ethyl acetate or a mixed solvent of ethyl acetate and 1,2-propanediol.

More preferably, considering that ethyl acetate is volatile and has weak polarity so that it is slightly difficult to uniformly disperse in the racemic mandelic acid nicotine salt gelling agent of medium polarity (for example, heating is required), so The organic solvent is more preferably a mixed solvent of ethyl acetate and 1,2-propanediol.

Described organic solvent selects the mixed solvent of ethyl acetate and 1,2-propanediol, has the following reasons: the one, the gelling agent overall performance is medium polarity, easy and medium polarity solvent-ethyl acetate and 1,2- The mixed solvent of propylene glycol forms a homogeneous system when heated; the second is that the medium-polarity fragrance substance has a large solubility in the mixed solvent of medium-polarity solvent-ethyl acetate and 1,2-propylene glycol; the third is that the gelling agent has medium polarity , it is easy to form a gel in a mixed solvent of similar polar solvent ethyl acetate and 1,2-propanediol, so as to avoid phase separation and gelation failure during cooling and gelation; four is that 1,2-propanediol itself can as a fumigant.

More preferably, in the mixed solvent of ethyl acetate and 1,2-propanediol, the volume ratio of ethyl acetate and 1,2-propanediol is (2:8)～(4:6), at this moment, to gelling agent and The solubility of fragrance substances is better.

The key or difficulty in the preparation process of the present invention is to avoid the formation of nicotine salts, and the following methods are mainly used to avoid salt formation:

1. The present invention reduces the ionization reaction of carboxylic acid in racemic mandelic acid to avoid forming nicotine salt by using organic solvent instead of water;

2. In the conventional method for preparing nicotine salt: direct heating to promote acid-base neutralization reaction. The invention adopts reflux and rotary steaming to prevent violent salt-forming reaction to prepare the gelling agent.

3. In conventional methods for preparing nicotine salts: Freeze-drying is used to quickly remove free or crystalline water contained in nicotine salts. The invention adopts rotary steaming means to remove the solvent ethanol in the reaction system to obtain the gelling agent.

Preferably, the fragrance substance is selected from the group consisting of: jasmone, anisone, gingerone, muscone, civetone, nerolidol, farnesol, β-caryophyllenol, β-santalol, α-santalol, Jasmonal, Vanillin, Ethyl Vanillin, Piperonal, Cinnamaldehyde, Methyl Laurate, Ethyl Laurate, Methyl Myristate, Ethyl Myristate, Geranyl Benzoate, Aryl Benzoate One or more of camphor, phenylacetic acid, and β-caryophyllene.

The third aspect of the present invention provides the use of the gel containing flavor and racemic mandelic acid nicotine salt gelling agent described in the first aspect, and the gel is used in heat-not-burn cigarettes or electronic cigarettes.

Preferably, when the gel is used in heat-not-burn cigarettes, it will effectively prolong the release time of nicotine, make the physiological experience brought by nicotine more sustained, avoid the problem of leaching or moisture absorption of smoking agent, and also avoid Excessive loss of fragrance;

When the gel is used in electronic cigarettes, it can not only stabilize the flavoring ingredients and nicotine, but also ensure the synergistic release of the flavoring ingredients and nicotine during heating and atomization.

The way to use the gel in electronic cigarettes is to add nicotine salt gel microparticles into the smoke liquid solvent (smoke agent) system or smoke liquid or directly disperse the nicotine salt fragrance-carrying gel in the smoke liquid solvent ( Smoker) or e-liquid to form a uniform system, which not only stabilizes the aroma components and nicotine, but also ensures the synergistic release of aroma components and nicotine during heating and atomization.

Principle of the present invention is as follows:

The present invention obtains a gelling agent by selecting specific carboxylic acid racemic mandelic acid to react with nicotine, and controlling reaction conditions, such as solvent type, heating mode, post-treatment mode, reactant ratio and the like.

Supramolecular synthons, which constitute the supramolecular structural units that can form stable gels, are the key to the formation of the above-mentioned gelling agents. According to the concept of crystal engineering, if the same type of supramolecular interactions can be reliably and reproducibly formed between basic building blocks (molecules) with specific functional groups, then the non-covalent bonds connecting these basic building blocks are called supramolecular. molecular synthon. Increasing the hydrogen bonding sites is beneficial to the assembly of gelling agent molecules into a gel network.

Mandelic acid is DL-racemic mandelic acid, comprising an equimolar mixture of L(+)-D-mandelic acid and D(-)-L-mandelic acid. When 1mol L(+)-D-mandelic acid, 1mol D(-)-L-mandelic acid and 1mol nicotine undergo supramolecular interaction, a supramolecular structural unit and a 1-dimensional hydrogen bond network as shown in Figure 2 are formed, wherein , in addition to the face-to-face π-π stacking interaction between the pyridine ring and the benzene ring (7 in Figure 2), there is also the π-π stacking interaction between the carboxylic acid benzene rings (8 in Figure 2), and finally the corresponding racemic mandelic acid nicotine salt gelling agent (pH ratio 2:1).

According to molecular engineering theory, gelation needs to meet the following three conditions: (1) strong and directional supramolecular interaction promotes the aggregation of gelling agent molecules to form fibers; (2) the ability to entangle or interweave to form fibers (ie the ability to form SAFINs); (3) factors that prevent pure crystallization of gelling agents. Various hydrogen-bonding supramolecular synthons as described above facilitate (1) and (2), while long hydrocarbon chains can facilitate (3).

The determination method of the critical gel concentration CGC is the test tube inversion method: add gelling agents of different qualities into a test tube with 1g of solvent, heat until the gelling agent is completely melted, let it stand at room temperature, and invert the test tube if the substance does not condense. Deformation is considered to form a gel, and the minimum mass percentage of the gelling agent required to form the gel is the critical gelling concentration of the gelling agent.

The sol-gel transition temperature T _gel is measured by the falling ball method: 0.5 g of gel is placed in a test tube (15 mm x 100 mm), and glass beads with a mass of 214.6 mg are placed on the surface of the gel. Submerge the test tube in an oil bath and heat it. When the glass ball falls to the bottom of the test tube, record the temperature as T _gel .

Compared with the prior art, the present invention has the following beneficial effects:

1. The present invention uses racemic mandelic acid and nicotine for the first time to prepare a gelling agent and fragrance-carrying supramolecular gel with a supramolecular network structure, which realizes the co-fixation and synergistic release of nicotine and aroma components .

According to calculation, the critical gel concentration CGC of the gelling agent is 0.77wt%, that is, when the gel is formed, the minimum mass fraction of the gelling agent in the gel is 0.77wt%. According to calculation, the sol-gel transition temperature (T _gel ) of the gelling agent is 92°C. Under atmospheric pressure, if the temperature is above 92°C, the substance is in a sol or solution state, and below 92°C, the substance is in a gel state. Due to the inherent thermal reversibility of supramolecular gels, flavoring substances (especially semi-volatile flavoring substances) are encapsulated inside by the nicotine salt gel network, and only when the heating temperature ≥ T _gel , the gel will melt into a sol Or solution, and when the temperature is lower than T _gel , the molten sol or solution undergoes reversible gelation and returns to a gel state. In this way, the fragrance substances are stably fixed inside the gel network at normal temperature, which effectively increases the storage stability of the fragrance-causing ingredients.

2. The inherent high loading rate of the supramolecular gel to the solvent (smoke agent) and the aroma-generating substances dissolved in it can make up for the problem of insufficient aroma and smoke production of heated cigarettes, and realize the optimization of the aroma and smoke production. Effective replenishment; especially the semi-volatile aroma substances are fixed in the nicotine salt gel that releases nicotine in the high-temperature section, which can reduce the volatility loss of aroma in the preheating stage or low-temperature heating stage and supplement the decaying aroma in the middle and late stages of smoking .

3. Unlike conventional polycarboxylic acid nicotine salts, in the racemic mandelic acid nicotine salt gelling agent of the present invention, carboxyl groups form heterogeneous synthons with pyridine nitrogen and pyrrole nitrogen, and the supramolecular structural units formed by these synthons self-assemble In order to stabilize the fiber network, the number of free carboxyl groups is reduced or even there is no free carboxyl group, which inhibits the chance of volatile monocarboxylic acid produced by dehydration and decarboxylation in the preheating stage or low-temperature heating stage of heated cigarettes, and reduces the slow rate caused by moisture and acidity. Accumulation results in a small amount of smoke in the front of the puff, burning the mouth with smoke, and obvious sourness.

4. One of the inherent characteristics of supramolecular gels is that the content of the gelling agent used is extremely small, while the content of the gel-loaded substance is extremely large (for example, one molecule of gelling agent can combine thousands of molecules of solvent). Thus, the net effect is that a small amount of nicotine salt gelling agent can bind to the aromatizing ingredient dissolved in the solvent by immobilizing a large amount of solvent. In the field of heated cigarettes, such advantages are reflected in: due to the low coating rate of traditional coating liquid, it is often necessary to increase the amount of coating liquid or add tobacco extract to obtain sufficient aroma and smoke, while gel Due to the high content of the smoke-generating agent and aroma-inducing components loaded, the application amount of the gel will be lower than that of the simple application of the coating solution, which is beneficial to reduce raw materials and manufacturing costs.

5. In addition, the solvent 1,2-propanediol used in the gel of the present invention is itself a fuming agent, and the fuming agent is locked inside the gel at room temperature so that the problem of fuming agent leaching or moisture absorption is not easy to occur, and it also avoids the fragrance lost too quickly.

6. Since the structure of nicotine salt gel is more stable than that of pure nicotine salt, the upper limit of nicotine release temperature will exceed the upper limit of nicotine release temperature in conventional nicotine salt, which can reduce the release loss of nicotine before 210 ℃, and effectively Extend the release time of nicotine to make the physiological feeling brought by nicotine more sustainable.

7. Due to the inherent thermal reversibility of the supramolecular gel, when applying the gel to the reconstituted tobacco leaves for heating cigarettes, it is only necessary to heat and melt the gel into a sol or solution and apply it to the reconstituted tobacco leaves, and then cool to condense. Gelling and combining with reconstituted tobacco leaves makes the processing of reconstituted tobacco leaves synchronize with the formation of gel and reduces the number of procedures.

8. The use of nicotine salt gel as the carrier of flavoring substances and smoke-generating agents lowers the requirements for the base loading function of reconstituted tobacco leaves and reduces the use of a large number of loading fillers.

9. For thick pulp reconstituted tobacco leaves, even though a high amount of moisture needs to be removed during drying, since the aroma substances and smoke-generating agents are fixed inside the gel, low-temperature multi-stage drying and other measures can effectively remove moisture while removing moisture. Avoid loss of aroma substances and smokers.

10. Conventional reconstituted tobacco leaves have a large amount of fuming agent applied to their surface, so the surface of reconstituted tobacco leaves has high viscosity and poor elasticity, which puts higher requirements on the subsequent shredding process, and the gel used is to encapsulate the fuming agent inside or reduce The amount of additional fuming agent is reduced, the surface viscosity of reconstituted tobacco leaves is reduced, and the inherent viscoelasticity of the gel also increases the elasticity of reconstituted tobacco leaves, which is beneficial to subsequent shredding processing.

11. Since the raw materials for preparing the gelling agent are nicotine and carboxylic acid, and no other components are added, it will not leave residue after heating or adhere to the heating element to produce bad smell.

12. When the nicotine salt gel of the present invention is used in electronic cigarettes, by adding nicotine salt gel microparticles to the smoke liquid solvent (smoke agent) system or smoke liquid, or directly dispersing the nicotine salt fragrance-carrying gel in the A homogeneous system is formed in the e-liquid solvent (smoking agent) or e-liquid, which not only stabilizes the aroma components and nicotine, but also ensures the synergistic release of the aroma components and nicotine during heating and atomization. In addition, by adjusting the adaptability of the nicotine salt gelling agent and the loaded flavor substances, the obtained nicotine salt supramolecular fragrance-loaded gel has the characteristics of high fragrance loading, high solvent (smoke agent) loading, and thermal reversibility. . The present invention utilizes the gel medium to connect the originally separated nicotine salt system and flavor and fragrance system on the one hand and form a new material form (gel); on the other hand, it combines the originally separated physiological satisfaction and relaxation with The smoking taste of the characteristic taste is linked to form a new comprehensive sensory experience (due to the synergistic release of nicotine and flavor substances). Through the reorganization of the material level and the sensory level, the nicotine and aroma components are released synergistically, so as to obtain a synergistic sensory experience.

13. The known temperature ranges for nicotine salts to release nicotine include two intervals of 110-125°C and 160-210°C. When the nicotine salt gel of the present invention is used to replace nicotine salt in electronic cigarettes, due to the structural stability of the supramolecular gel itself, nicotine is equivalent to being fixed by the gel structure, preventing the rapid release of nicotine, and the release temperature of nicotine The T _nic range is higher than that of conventional nicotine salts and is close to or consistent with the working temperature of electronic cigarettes, which improves the inhalation of nicotine at the working temperature of electronic cigarettes and lasts longer for the release of nicotine.

14. The specific fragrance-carrying supramolecular gel system of the present invention comprehensively matches factors such as thermal stability of nicotine salt gelling agent, nicotine release temperature range, volatility of flavor substances fixed in the gel, and solvent properties. In particular, the present invention fixes the semi-volatile aroma substances in the racemic mandelic acid nicotine salt gel with good thermal stability (large T _gel value) and releases nicotine (larger T _nic value) in the high temperature range, which can overcome The defect that the semi-volatile aroma substances are released in a large amount in the first part of the inhalation and the aroma is weak in the latter part of the inhalation.

15. When the nicotine salt gel of the present invention is used in electronic cigarettes, when smoking is stopped or electronic cigarettes are not used, due to the thermal reversibility of the gel, the molten gel condenses and gels, even if nicotine passes through The recovery of the nicotine salt gelling agent network stabilizes again, fixes the flavoring substances in the gel again and stabilizes, reducing the loss of nicotine and flavoring substances in the heating and cooling process of the electronic cigarette.

16. The interchange between gel and solution/sol phases is only related to the disassembly and assembly of supramolecular structural units, and the chemical composition will not change during the phase transition process, which contributes to the stable and consistent sensory experience of electronic cigarettes.

17. The reconstituted tobacco leaves loaded with the coating solution of the present invention are of the type with high aroma loading, high smoke generation and low coating amount. The traditional reconstituted tobacco leaves are of the type with low aroma loading, low smoke generation and high coating amount. The specific performance is: when the coating solution of the present invention is cooled and gelled, the fragrance substance and the fuming agent are locked in the gel and separated from the water, and the water outside the gel can be removed during subsequent heating and drying to control the water content , and to avoid the loss of fragrance in the gel, the amount of coating liquid applied to achieve the desired amount of aroma and smoke is lower. Using a high proportion of gel coating solution (referring to the high proportion of gel in the coating solution, that is, the coating solution is dominated by gel, so that the coating amount will be reduced) can make full use of the fixed fragrance and smoke agent At the same time, the coating amount is greatly reduced and the utilization rate of the coating solution is increased, and the new HNB reconstituted tobacco leaves with high aroma and high smoke production are different from the existing HNB reconstituted tobacco leaves, reflecting the application value of the gel. Flavors and fuming agents in traditional coating solutions have no medium to lock them. When the moisture content is controlled by heating and drying, the fragrances, moisture and fuming agents are all in an open state, which removes both moisture and part of the fragrance and fuming agents. Therefore, it is necessary to add high-content spices (such as 7%-8%) and smokers (such as 20%) to make up for the loss. As a result, the amount of coating liquid applied to achieve the required aroma and smoke is higher, and the waste is less. big.

Description of drawings

Figure 1 is a schematic diagram of the pyridine-carboxylic acid synthon of the present invention.

Fig. 2 is the supramolecular structural unit and fiber network of racemic mandelic acid nicotine salt of the present invention.

Detailed ways

The present invention will be described below in conjunction with specific examples, but the embodiments of the present invention are not limited thereto. For the experimental methods that do not indicate specific conditions in the examples, generally according to the conventional conditions and the conditions described in the manual, or according to the conditions suggested by the manufacturer, the general equipment, materials, reagents, etc. obtained commercially. The raw materials needed in the following examples and comparative examples are all commercially available.

Example 1

A method for preparing a supramolecular gel for synergistically releasing nicotine and flavoring ingredients, comprising the steps of:

Step 1, preparation of gelling agent: racemic mandelic acid and nicotine are respectively dissolved in the mixed solvent of water and isopropanol by 2:1 molar ratio, racemic mandelic acid and the water and isopropanol that dissolve it The mass volume ratio of the mixed solvent is 1g:28mL, the mass volume ratio of nicotine to the water and isopropanol that dissolves it is 1g:210mL, stirring at room temperature accelerates the dissolution of nicotine, because mandelic acid is easily soluble in hot water, heating and stirring Dissolving racemic mandelic acid to obtain nicotine solution and racemic mandelic acid solution respectively, then fully heating and mixing the above two solutions to obtain a mixed solution, heating is conducive to the full effect of acid and alkali, and then raising the temperature of the mixed solution to reflux , reacted for more than 30 minutes, 130mbar, 53 ° C rotary steaming, and then the product obtained by rotary steaming was dried at 36 ° C for 24 hours, to obtain racemic mandelic acid nicotine salt gelling agent. In the mixed solvent of water and isopropanol, the volume ratio of water and isopropanol is 1:5.

Step 2, preparation of gel:

The aroma substance was dissolved in a mixed solvent of ethyl acetate and 1,2-propanediol to obtain a solvent containing the aroma substance, and the mass volume ratio of the aroma substance to the mixed solvent of ethyl acetate and 1,2-propanediol was 1g:22mL. In the mixed solvent of ethyl acetate and 1,2-propanediol, the volume ratio of ethyl acetate and 1,2-propanediol is 3:7.

The racemic mandelic acid nicotine salt gelling agent prepared in step 1 of taking a certain amount of 0.85g is placed in the test bottle, and 20mL of the fragrance-containing substance solvent is taken (illustration: when the amount of the gelling agent is constant, different volumes of gelling agent can be fixed. Solvent, here 20mL refers to the maximum amount of solvent that can be fixed by 0.85g gelling agent) is added into the test bottle, dissolved by heating and stirring or ultrasonic wave, and then left in an ice-water bath at 2°C for 2.5h to form a fragrance-carrying supramolecular gel.

The supramolecular structural unit and 1-dimensional hydrogen bond network of the racemic mandelic nicotine salt gelling agent formed in Step 1 are shown in Figure 2, and each synthon has been marked in Figure 2: 2 is the pyridine nitrogen-carboxylic acid heterogeneous Synthon, 3 is the pyrrole nitrogen-carboxylic acid charge-assisted hydrogen bond (N ⁺ ... HO ^- ) heterogeneous synthon, 4 is the intermolecular alcoholic hydroxyl hydrogen bond (OH...O), 7 is between the pyridine ring and the benzene ring The face-to-face π-π stacking interaction of 8 is the π-π stacking interaction between carboxylic acid benzene rings.

Example 2

This example provides the application of the fragrance-loaded supramolecular gel prepared in Example 1 of the present invention in heating cigarettes

The nicotine salt supramolecular gel can be respectively applied in the manufacturing process of the reconstituted tobacco leaves for paper-making heated cigarettes and the reconstituted tobacco leaves for thick-pulp heated cigarettes, and a single gel or different types of mixed gels can be applied according to actual conditions.

Reconstituted tobacco leaves for paper-making heated cigarettes:

Method 1: Add the fragrance-carrying supramolecular gel prepared in Example 1 to a certain amount of fuming agent (1,2-propanediol, glycerin or a mixture of the two in a certain proportion), the quality of the fragrance-carrying supramolecular gel and the fuming agent The ratio is 4.5:1, when the temperature rises to 95°C, the gel melts into a sol state or a solution, and is uniformly mixed to form a mixed coating solution containing molten gel and fuming agent, and the mixed coating solution is sprayed on the paper by spraying process Tobacco sheet base prepared by method. Cool the reconstituted tobacco leaves to which the mixed coating liquid has been applied to room temperature, so that the melted gel is gelled and uniformly dispersed in the smoking agent. After one or more times of drying, the moisture in the reconstituted tobacco leaves is removed to a suitable moisture content, and then shredded and rolled.

The above-mentioned preparation process of the mixed coating liquid containing molten gel and smoke-generating agent has the following characteristics:

1. Another preparation method is to heat the fragrance-carrying supramolecular gel until it is melted and transformed into a sol state or a solution, and then add a certain amount of hot fuming agent. This solution is not adopted in this embodiment, in order to avoid the formation of a sol-gel mixture due to the condensation of the melted gel after the fuming agent is not fully melted due to cooling, and also to reduce the energy consumption of the two-step heating;

2. The mass ratio of spices and smokers in conventional heated cigarettes is usually 1:4-1:2.5, but a large amount of flavoring substances will be lost in the actual production process, and the final actual ratio is lower than the above ratio. The gel of Example 1 itself fixes the fuming agent, which can greatly reduce the amount of additional fuming agent. At the same time, because the fragrance substance is fixed by the gel, the loss of the fragrance substance in the subsequent drying and water removal process is reduced. Gel ratio to increase the fragrance loading.

Method 2: Heat the fragrance-loaded supramolecular gel prepared in Example 1 to 95°C to melt and transform into a sol state or a solution, according to the amount of smoke required for the final product, the amount of fuming agent fixed in the gel itself, and the melted gel Viscosity, the melted gel is directly used as a coating solution and sprayed on the tobacco sheet base prepared by papermaking method by spraying process. Cooling the reconstituted tobacco leaves to which the coating liquid has been applied is cooled to room temperature, so that the melted gel is gelled and uniformly dispersed on the surface of the reconstituted tobacco leaves. It is then shredded and rolled.

Reconstituted tobacco leaves for heated cigarettes with thick pulp method:

Method 1: The application of the above-mentioned gel is concentrated in the subsequent stages of molding (casting) and drying. Specifically: after the reconstituted tobacco leaves are formed by the thick slurry method and dried to remove high moisture, the above-mentioned gel is heated to 95°C to melt and transform into a sol state or a solution, which is directly used as a coating liquid and sprayed on the reconstituted tobacco leaves by spraying;

Or add the fragrance-carrying supramolecular gel prepared in Example 1 to a certain amount of fuming agent (1,2-propanediol, glycerin or a mixture of the two in a certain proportion), and the mass ratio of the fragrance-carrying supramolecular gel to the fuming agent is 5:1, heat up to 95°C, the gel melts into a sol state or a solution, mixes evenly to make a mixed coating liquid containing molten gel and smoke agent, and sprays the coating liquid on the reconstituted tobacco leaves by spraying process. Cooling the reconstituted tobacco leaves to which the coating solution has been applied is cooled to room temperature, so that the melted gel is gelled and evenly dispersed on the surface of the reconstituted tobacco leaves or in the smoking agent. After one or more times of drying, the moisture in the reconstituted tobacco leaves is removed to a suitable moisture content, and then shredded and rolled.

Because the moisture content of the reconstituted tobacco leaves by the thick pulp method is relatively high, and the amount of smoke is not high, the proportion of the added smoke agent is appropriately increased here compared with the papermaking method.

Method 2: use the fragrance-loaded supramolecular gel prepared in Example 1 as a component of the slurry. Specifically: mix tobacco raw materials, adhesives, fuming agents, etc., and grind them into powders of a certain mesh size, then add a certain amount of water, and add the fragrance-carrying supramolecular gel prepared in Example 1 at 50-60°C, Stir well to form a homogeneous slurry. Then spread it evenly on the circulating metal belt, and raise the temperature to 90°C (the temperature of the thick slurry method can be slightly lower than the sol-gel transition temperature, because the heating is on a metal belt, and the temperature rises quickly) to melt the gel in the slurry Finally, the temperature is lowered step by step, the molten gel is gelatinized, and the slurry is dried, dehydrated and solidified in multiple stages at the same time, and finally stripped to make reconstituted tobacco leaves.

The reasons are as follows: firstly, mixing at 50-60°C is a common temperature condition for pulping, which can ensure the mixing uniformity of the slurry; in the subsequent manufacturing process, the slurry mixed with gel is spread on the metal belt, which increases the size of the gel. The contact area with the heating area can ensure the rapid and uniform melting of the gel at 90°C. On the one hand, the gel can be evenly distributed in the reconstituted tobacco leaves, and on the other hand, the loss of aroma substances in this process is reduced; the subsequent step-by-step cooling ensures Dehydration and gelation are carried out simultaneously and uniformly.

Example 3

This example provides the application of the fragrance-loaded supramolecular gel prepared in Example 1 in electronic cigarettes.

The nicotine salt supramolecular gel can be applied in electronic cigarettes in two ways, and a single gel or different types of mixed gels can be used according to actual conditions.

Method 1: Dry the fragrance-carrying supramolecular gel prepared in Example 1 above at a constant temperature in an oven at 40°C for 24-36 hours, grind the dried gel into uniform micro-particles, and add a certain amount of e-cigarette gel in a certain proportion. Fully stir in the fuming agent, the fuming agent is a mixed solvent of glycerin and 1,2-propylene glycol 1:1 (volume ratio), the mass ratio of the fragrance-carrying supramolecular gel to the fuming agent is 1:120, mix well and serve as The flavor-containing gel smoking agent or as an auxiliary material is directly added to the finished e-liquid and mixed uniformly as the flavor-containing gel e-liquid.

The smoking agent in the electronic cigarette is equivalent to the dispersion medium of the gel, and the proportion of the smoking agent should not be too low. On the premise of ensuring the amount of aroma and smoke, the amount of gel added should be reduced as much as possible.

Method 2: Use the gel itself immobilized with a large amount of 1,2-propanediol as a gel-state atomization material.

The gel-containing e-liquid mentioned above undergoes gel melting at the macroscopic level under the heating temperature of the electronic cigarette, while at the microscopic level, the dismantling of the gel network, the separation of supramolecular structural units, and the rupture of supramolecular synthons occur. The nicotine locked in the gel is released and inhaled with the synergistic release of flavoring substances and smoking agents; when the puff is stopped or not used, the molten gel regels due to the thermally reversible properties of the supramolecular gel Through chemical reaction, nicotine and carboxylic acid molecules recombine to form supramolecular synthons, which in turn form supramolecular structural units, and these structural units are further assembled into a fiber network to fix condensed flavor substances and smokers in it.

Example 4

A method for preparing a supramolecular gel for synergistically releasing nicotine and flavoring ingredients, comprising the steps of:

Step 1, preparation of gelling agent: racemic mandelic acid and nicotine are respectively dissolved in the mixed solvent of water and isopropanol by 2:1 molar ratio, racemic mandelic acid and the water and isopropanol that dissolve it The mixed solvent mass volume ratio of nicotine is 1g:25mL, the mixed solvent mass volume ratio of nicotine and the water that dissolves it and isopropanol is 1g:250mL, stir at room temperature until completely dissolving, obtain racemic mandelic acid solution and nicotine respectively Solution, and then the above two solutions are fully mixed to obtain a mixed solution, the mixed solution is heated to reflux, reacted for more than 30min, 135mbar, 50 ° C rotary steaming, and then the rotary steamed product was dried at 36 ° C for 25 hours, A racemic mandelic acid nicotine salt gelling agent is obtained. In the mixed solvent of water and isopropanol, the volume ratio of water and isopropanol is 1:6.

Step 2, preparation of gel:

The fragrance substance was dissolved in ethyl acetate to obtain a fragrance substance-containing solvent, and the mass volume ratio of the fragrance substance to ethyl acetate was 1g:22mL. The racemic mandelic acid nicotine salt gelling agent prepared in step 1 of taking a certain amount of 0.85g is placed in the test bottle, and 20mL of the fragrance-containing substance solvent is taken (illustration: when the amount of the gelling agent is constant, different volumes of gelling agent can be fixed. Solvent, here 20mL refers to the maximum amount of solvent that can be fixed by 0.85g gelling agent) is added into the test bottle, dissolved by heating and stirring or ultrasonic wave, and then left in an ice-water bath at 2°C for 2.5h to form a fragrance-carrying supramolecular gel.

Claims (5)

1. A method for preparing a supramolecular gel for the synergistic release of nicotine and flavor components, comprising the steps of:

step 1, preparing a gelling agent: respectively dissolving racemic mandelic acid and nicotine into a mixed solvent of water and isopropanol according to a molar ratio of 2:1, stirring at room temperature until the racemic mandelic acid and the nicotine are completely dissolved to respectively obtain racemic mandelic acid solution and nicotine solution, then fully mixing the two solutions to obtain a mixed solution, heating the mixed solution to reflux, reacting for more than 30min, performing rotary evaporation, and drying a product obtained by rotary evaporation at 30-40 ℃ for 20 to 30h to obtain a racemic mandelic acid nicotine salt gelling agent;

the racemic mandelate nicotine salt gelling agent is a three-dimensional network structure formed by self-assembly of one-dimensional fibers, the one-dimensional fiber structure is formed by connecting a plurality of racemic mandelate nicotine salt supramolecular structural units formed between racemic mandelic acid and nicotine, and the connection between the racemic mandelate nicotine salt supramolecular structural units is as follows:

；

step 2, preparation of gel:

dissolving the fragrant substance with organic solvent to obtain a fragrant substance-containing solvent; then adding the flavor-containing substance into the racemic mandelic acid nicotine salt gelling agent obtained in step 1, dissolving the substance by heating and stirring or ultrasonic treatment, and then standing in an ice water bath to form a gel.

2. The preparation method according to claim 1, wherein in the step 1, the volume content of water in the mixed solvent of water and isopropanol is less than 20%; the mass volume ratio of the racemic mandelic acid to the mixed solvent of water and isopropanol is 1g to 20 to 30mL, the mass volume ratio of the nicotine to the mixed solvent of water and isopropanol is 1g to 100 to 300mL, the rotary evaporation temperature is 50-60 ℃, and the rotary evaporation pressure is 120-140mbar.

3. The production method according to claim 1, wherein in step 2, the mass volume ratio of the flavor substance to the organic solvent is 1g to 30mL, the mass volume ratio of the racemic nicotine mandelate gelling agent to the flavor-containing solvent is 1g to 30mL, the temperature of the ice water bath is 4 ℃, and the standing time in the ice water bath is 1 to 3h.

4. The method for preparing according to claim 1, wherein the fragrant substance is selected from the group consisting of: one or more of jasmone, anisyl ketone, zingerone, muscone, civetone, nerolidol, farnesol, beta-caryophyllenol, beta-santalol, alpha-santalol, jasmal, vanillin, ethyl vanillin, piperonal, cinnamaldehyde, methyl laurate, ethyl laurate, methyl myristate, ethyl myristate, geranyl benzoate, linalyl benzoate, phenylacetic acid and beta-caryophyllene.

5. The method according to claim 1, wherein the organic solvent is ethyl acetate or a mixed solvent of ethyl acetate and 1,2-propanediol.

Images