METHOD FOR ADJUSTING THE NICOTINE CONTENT IN AN E-CIGARETTE AEROSOL

Description

[0001] The present invention relates to a method for adjusting the nicotine content of an aerosol in an inhaler, comprising the following steps: a supply step in which at least one liquid having a first nicotine content is supplied from a vaporizer tank to an electric vaporizer, a vaporization step in which the at least one liquid is vaporized to produce an aerosol, a dispensing step in which a final aerosol, which consists of the combination of all aerosols formed in the inhaler from the at least one liquid, is dispensed from the inhaler to a user.

[0002] Inhalers, particularly in the form of electronic cigarettes (hereinafter referred to as e-cigarettes), are used in the medical field and particularly in the consumer goods industry. E-cigarettes are enjoying great popularity and are increasingly replacing the consumption of conventional tobacco products. Unlike conventional tobacco products, in which the consumer inhales the smoke from burning plant parts, particularly tobacco, no combustion of plant parts takes place in e-cigarettes. Instead, a liquid, usually referred to as e-liquid, is vaporized in a vaporizer unit and mixed with air in a flow channel, creating an aerosol, mist, or aerosol-vapor mixture that the consumer inhales.

[0003] The liquid is stored on or in the atomizer cartridge. Various blends with different components of the same or different vapor densities are used. A typical blend for use in an e-cigarette, for example, contains components of glycerin and propylene glycol, enriched with nicotine, and optionally with almost any flavoring.

[0004] Just as with conventional cigarettes, the nicotine content of a cigarette has a maximum limit, so too does the nicotine content of an e-cigarette's liquid, which may not be exceeded. In the EU, the nicotine content of e-cigarette liquids is limited to a concentration of 20 mg / ml. According to 2014 / 40 / EU, this limit only applies to liquids. The nicotine concentration of the

[0005] There is no limit to the aerosols produced by evaporation.

[0006] US 2015 / 344456 A1 (DULL GARY M [US] ET AL) December 3, 2015 discloses a method for adjusting the nicotine content of an aerosol in an inhaler. This document uses nicotine salt to increase the consumer's nicotine intake compared to free base nicotine.

[0007] According to HARVANKO ARIT M ET AL: "Characterization of Nicotine Salts in 23 Electronic Cigarette Refill Liquids", NICOTINE & TOBACCO RESEARCH, Vol. 22, No. 7, June 12, 2020 (2020-06-12), pages 1239-1243, the protonated form of nicotine is perceived as less irritating by consumers.

[0008] ALLOCK et al.: "Trendy e-cigarettes enter Europe: chemical characterization of JUUL pods and its aerosols", ARCHIVES OF TOXICOLOGY, SPRINGER, DE, Vol. 94, No. 6, March 18, 2020 (2020-03-18), pages 1985-1994, reveals that the nicotine concentration in the e-liquids of the recently launched European version is limited to below 20 mg / ml to comply with European law. This limit can potentially be circumvented through technical adaptations that increase vaporization and thus nicotine delivery.

[0009] The maximum permitted nicotine concentration in e-cigarette liquids in the EU is comparatively low. In the US, however, e-cigarette cartridges filled with liquids with a 5% nicotine content are sold. The popularity and the pleasant, tobacco-like experience perceived by e-cigarette smokers are due not only to the nicotine salts in the liquids sold in the US, but also to the high concentration, which can achieve a rapid increase in blood nicotine concentration comparable to that of tobacco cigarettes. Achieving a similar blood nicotine concentration with e-cigarette liquids that comply with EU regulations is desirable.

[0010] The object of the present invention is therefore to provide a method that enables an increased blood nicotine concentration compared to that achievable with conventional liquids and at the same time complies with the provisions of 2014 / 40 / EU.

[0011] This object is achieved in a method of the type mentioned at the outset in that at least one of the at least one liquid has a precursor substance which can be converted into nicotine by chemical reaction, and the method further comprises a nicotine production step in which the precursor substance is converted into nicotine by chemical reaction, so that the final aerosol has a second nicotine content which is higher than the first nicotine content.

[0012] Within the scope of the present invention, it was discovered that it is possible to increase the nicotine content in the generated aerosol by adding at least one substance to the liquid that only converts into nicotine during the formation of the aerosol. This allows the nicotine content of the liquid to be kept within the legally prescribed limits, while at the same time the aerosol inhaled by the consumer has a higher nicotine content desired by the consumer. The precursor substance is converted during the process and continues to reach the consumer in the aerosol as nicotine.

[0013] In the present invention, the term aerosol refers to the vapor phase that arises through evaporation of the liquid and is also intended to include mist, vapor or mixtures of aerosol, mist and / or vapor, ie the gaseous phase can contain solid and / or liquid particles.

[0014] Any chemical reaction is conceivable for converting the precursor substance into nicotine: substitutions, additions, eliminations, rearrangements, radical reactions, or acid-base reactions. Oxidation or, in particular, reduction are particularly preferred.

[0015] Chemical reduction is the reverse reaction of oxidation, in which a reducing agent donates electrons to an already oxidized substance (thus "reducing" it).

[0016] The conversion of the precursor substance to nicotine preferably takes place using a catalyst. The use of a catalyst enables reactions that would be impossible or uneconomical without the catalyst, for example, because too much energy would have to be supplied to initiate and / or complete the reaction. The catalyst lowers the required activation energy to a certain level through an intermediate reaction with the precursor substance. This makes the reaction more economical or even possible in the first place, because without the reduction, other competing reactions would occur that would not allow the desired reaction to occur or would only allow it to occur with very low yields.

[0017] Furthermore, it is particularly preferred if the conversion of the precursor substance to nicotine is carried out using an enzyme. Enzymes are proteins that typically selectively catalyze a specific reaction. Enzymes can also enable the conversion reaction of the precursor substance to nicotine to take place under mild conditions. Nicotine has the following structural formula:

[0018] Various compounds are conceivable as precursor substances. In one advantageous embodiment, nicotine glucuronide or nornicotine can be used as a precursor substance. The former can be converted into nicotine using β-glucuronide, especially immobilized on a filter or column, while the latter can be converted into nicotine by reaction with methyltransferase. Enzymes are therefore used here. Cotinine or nicotine N'-oxide is particularly preferred as the precursor substance. Both compounds can be converted into nicotine in a reduction reaction. Cotinine occurs as an alkaloid in tobacco plants. The structural formulas of cotinine and nicotine N'-oxide are shown below:

[0019] The reduction of cotinine or nicotine N'-oxide is preferably carried out by catalytic hydrogenation, using lithium alanate (LiAlH 4 ) in polar protic solvents, or using other zinc hydride complexes. In this way, the reduction can be accomplished under mild conditions.

[0020] The precursor substance is preferably present in an amount such that a nicotine content of at least 30 mg / ml, preferably in particular at least 40 mg / ml and particularly preferably at least 50 mg / ml is achieved in the aerosol.

[0021] With the present invention, it is also possible to use liquids that do not contain any nicotine, but only precursor substances, so that all of the nicotine is only present in the aerosol.

[0022] The reactant can be present as a liquid in the liquid. Alternatively, the reactant can be a solid. It can either be a solid in its own right or be converted into a solid by freeze-drying.

[0023] In another particularly preferred embodiment, the reactant is provided in a contact element, and in the nicotine generation step, the precursor substance is brought into contact with the reactant in the contact element. Filters, as well as grid structures, are particularly suitable as such a contact element. These are inserted into the air duct of an e-cigarette and, thanks to their large surface area, ensure intensive contact between the aerosol, and in particular the precursor substance contained therein, and the reactant contained in the filter. For solid reactants or reactants solidified by lyophilization (freeze-drying), a preferred embodiment involves the application of nano- or microparticles in order to achieve the largest possible surface area.

[0024] For liquid reactants, a preferred embodiment involves the use of a spray system to load the aerosol with the respective liquid reactant. An alternative preferred embodiment works with a filter and a semi-permeable membrane, which ensures that the reactant escapes into the aerosol channel while preventing the aerosol from entering the filter. Alternatively, a pad impregnated with the liquid reactant can be attached to the air channel. The aerosol channel can be completely covered with the pad or partially, whereby any desired geometry can be used for the pad. Alternatively, a sieve or a grid can be used to absorb / absorb the liquid reactant. The aerosol penetrates the sieve or grid.In this way, the precursor substance to be reacted is reacted, whereby the enlarged surface enables particularly intensive contact of the reactant with the aerosol.

[0025] The attachments described above, in the form of pads, grids, or filters, are so-called "disposables," meaning they are consumables that must be disposed of and replaced after a certain number of puffs. For example, in the case of reducing agents, the redox potential is no longer present after a certain number of puffs. Preferably, the number of puffs is digitally recorded and integrated into an app for controlling the e-cigarette. This reminds or alerts the consumer of how many puffs are left and when a filter change is necessary.

[0026] The nicotine generation step can occur before the vaporization step, after the vaporization step, or simultaneously with the vaporization step. The nicotine precursor can therefore first be converted to nicotine and then transferred to the aerosol phase together with the remaining liquid. Alternatively, the conversion occurs during the formation of the aerosol. The conversion of the precursor substance to nicotine is particularly preferred when it occurs in the aerosol phase.

[0027] Furthermore, it is particularly preferred if the method is carried out in an inhaler with a vaporizer tank having at least two vaporizer tank chambers, whereby each vaporizer tank chamber can be assigned its own vaporizer. This makes it possible to convert different liquids with different ingredients into the aerosol phase separately from one another.

[0028] Such a design with more than one vaporizer tank chamber makes it particularly easy to work with multiple liquids, for example. A first liquid can contain nicotine, and the precursor substance can be contained either in the first liquid or in a second liquid. The precursor substance is particularly preferably contained in a second liquid. This way, the reaction for converting the precursor substance into nicotine can be carried out separately, and there is no risk that the conversion reaction could potentially cause undesirable reactions in the nicotine already present.

[0029] Furthermore, it is preferred that at least two liquids be used, with a first liquid containing nicotine and a second liquid containing a reactant that causes the conversion of the precursor substance into nicotine. The first liquid can contain nicotine and the precursor substance, with the precursor substance only reacting with the reactant when the two liquids come into contact.

[0030] In this described variant, the liquid containing nicotine and the precursor substance, and the liquid containing the reactant, are transferred separately into the aerosol phase. The reaction of the precursor substance with the reactant to form nicotine then occurs in the aerosol phase when the two aerosols—i.e., the aerosols from the first and the subsequent liquid—are combined. This combination allows the reaction of the precursor substance with the reactant to form nicotine. The final aerosol is created, which has the second nicotine content, which is higher than the first.

[0031] Particularly preferably, the second liquid contains both the precursor substance and the reactant. Alternatively, as described above, the reactant can also be provided in the form of a filter in the air duct for the second aerosol and convert the precursor substance as it passes through the filter in the aerosol.

[0032] In the variant described above, the nicotine-containing liquid and the liquid containing the precursor substance and, if applicable, the reactant are transferred separately into the aerosol phase. The reaction of the precursor substance with the reactant to form nicotine thus occurs separately. Only after the precursor substance has been converted to nicotine is the aerosol containing the newly produced nicotine combined with the aerosol of the liquid, which already contained nicotine to begin with.

[0033] In a preferred embodiment, a three-tank system is used. This allows the different substances to be stored separately from one another. In such a case, a first tank would contain a conventional liquid with the base nicotine content. This nicotine content would preferably correspond to the maximum permissible nicotine content. Another tank contains a liquid containing the precursor substance. Finally, a third tank contains a liquid containing the reactant and, if desired and / or necessary, a carrier substance. Suitable carrier substances include, in particular, conventional carrier substances such as water, propylene glycol (PG), and / or glycerin, especially vegetable glycerin ("vegan glycerols" - VG).

[0034] In a first step, the various liquids are formed into an aerosol. In a second step, the precursor substance is initially separately converted with the reactant to form nicotine. This prevents other components of the liquid from reacting uncontrollably with the reactant. For example, cotinine can first be reduced separately to nicotine, and this prevents other components of the liquid, such as flavorings, from also being reduced in an undesirable side reaction. A multi-chamber system preferably also has several separate vaporizers. In a third step, the aerosols are then mixed together to create the final aerosol with an increased nicotine content, which is ultimately inhaled by the consumer.

[0035] In another preferred embodiment, the conversion of the precursor substance to nicotine occurs before and / or between two e-cigarette sessions. The required amount of precursor substance is stored in the converted state and / or maintained in the aerosol phase by applying heat until the user begins the next session. This allows for reactions that require more time and energy to complete and deliver sufficient nicotine molecules to be used. If the next session is not scheduled for a longer period, the heating process is stopped to prevent unintended reactions from occurring due to the extended time.

[0036] Further useful and / or advantageous features and embodiments of the method for adjusting the nicotine content of an aerosol in an inhaler are set out in the dependent claims and the description. Particularly preferred embodiments are explained in more detail with reference to the accompanying drawing. The drawing shows: Fig. 1 is a schematic representation to illustrate the steps of a first variant of the method according to the invention, Fig. 2 is a schematic representation to illustrate the steps of a second variant of the method according to the invention, Figs. 3a and 3b are a schematic representation of the arrangement of a pad with reactant for carrying out the present invention and Figs. 4a and 4b are a schematic representation of the arrangement of a grid for receiving reactant for carrying out the present invention.

[0037] Fig. 1 shows a first vaporizer 1, which is connected to a first tank 2a and a second tank 2b. The first tank 2a contains a conventional liquid for an e-cigarette with a first nicotine content corresponding to the permissible nicotine content of 20 mg / ml, as well as a cotinine content. The second tank 2b contains a second liquid which contains a carrier and a reducing agent. The two liquids are vaporized to form an aerosol. This creates a first aerosol 3a with conventional e-liquid and cotinine, and a second aerosol 3b with a carrier and reducing agent. Both aerosols 3a, 3b are used in contact with each other, whereby the reducing agent reduces the cotinine to nicotine, thus increasing the nicotine content in the aerosol. The final aerosol 4 is created, which has a second nicotine content that is higher than the first nicotine content.

[0038] Fig. 2 shows an embodiment with three different tanks 2a, 2b, 2c, each of which is assigned a vaporizer 1a, 1b, 1c. The first tank 2a contains a conventional liquid with a base nicotine content corresponding to the maximum permissible nicotine content of a liquid. A second tank 2b contains a second liquid containing cotinine. Finally, the third tank 2c contains a third liquid containing the reducing agent and PG as a carrier substance.

[0039] In a first step, the various liquids are aerosolized. A first aerosol 3a containing nicotine and flavor, a second aerosol 3b containing cotinine, and a third aerosol 3c containing the reducing agent and PG are formed.

[0040] In a second step, the second aerosol 3b and the third aerosol 3c are mixed, and the cotinine contained in the second aerosol 3b is reduced to nicotine with the reducing agent contained in the third aerosol 3c. The second and third aerosols 3b and 3c are still separated from the first aerosol 3a. This prevents other components of the liquid, such as flavors contained together with the nicotine in the first aerosol 3a, from reacting uncontrollably with the reactant and also being reduced in an undesirable side reaction.

[0041] In a third step, the aerosols are then mixed together to create the final aerosol 4 with increased nicotine content, which is finally inhaled by the consumer.

[0042] Fig. 3a shows an embodiment of an air channel 5 of an inhaler for carrying out the method according to the invention in side view, Fig. 3b The same air duct 5 in plan view. A filter 6 containing the nanoparticulate reducing agent is arranged in the air duct 5. The cotinine-containing aerosol 3b passes through the filter 6 and thereby comes into contact with the reducing agent, so that the cotinine contained in the aerosol 3b is reduced to nicotine.

[0043] Fig. 4a shows a further embodiment of an air channel 5 of an inhaler for carrying out the method according to the invention in side view, Fig. 4b The same air duct 5 in plan view. A sieve or grid 7 is arranged in the air duct, in which the liquid reducing agent is contained. This sieve 7 is penetrated by the aerosol 3b, whereby the cotinine to be reduced can be comprehensively reduced due to the enlarged surface area and then reaches the consumer as nicotine in the aerosol 3b.

Claims

1. Method for adjusting the nicotine content of an aerosol in an inhaler, comprising the following steps: - a feeding step in which at least one liquid having a first nicotine content is fed from a vaporizer tank to an electric vaporizer, - a vaporizing step in which the at least one liquid is vaporized producing an aerosol, - a dispensing step in which a final aerosol consisting of the combination of all aerosols formed in the inhaler from the at least one liquid is dispensed from the inhaler to a user, characterized in that at least one of said at least one liquid comprises a precursor substance capable of being converted into nicotine by chemical reaction, and said method further comprises a nicotine generation step in which said precursor substance is converted into nicotine by chemical reaction so that said final aerosol has a second nicotine content higher than said first nicotine content.

2. Method according to claim 1, characterized in that the chemical reaction is an oxidation reaction or in particular a reduction reaction.

3. Method according to claim 1 or 2, characterized in that the nicotine generation step takes place before the vaporization step, after the vaporization step or simultaneously with the vaporization step.

4. Method according to at least one of the preceding claims, characterized in that the precursor substance is cotinine or nicotine N'-oxide.

5. Method according to at least one of claims 1 to 3, characterized in that the precursor substance is nicotine glucoronide or nornicotine.

6. Method according to at least one of the preceding claims, characterized in that the method is carried out in an inhaler having a vaporizer tank with at least two vaporizer tank chambers, it being possible for each vaporizer tank chamber to be assigned its own vaporizer.

7. Method according to at least one of the preceding claims, characterized in that a first liquid contains nicotine and that the precursor substance is contained either in the first liquid or in a second liquid.

8. Method according to at least one of the preceding claims, characterized in that at least two liquids are used, a first liquid containing nicotine and a further liquid containing a reactant which effects the conversion of the precursor substance into nicotine.

9. Method according to any one of claims 1 to 7, characterized in that the reactant is provided in a contact element and in that in the nicotine production step the precursor substance is brought into contact with the reactant in the contact element.

10. Method according to at least one of claims 1 to 9, characterized in that the conversion of the precursor substance into nicotine is carried out using a catalyst.

11. Method according to at least one of claims 1 to 10, characterized in that the conversion of the precursor substance into nicotine is carried out using an enzyme.