Liquid formulations and methods for preparing them, aerosol generating systems, cylinders for aerosol generating systems and aerosol generating devices

Abstract

The present application discloses a liquid formulation, a method for preparing the liquid formulation, an aerosol generating system, a cylinder for the aerosol generating system, and an aerosol generating device. The liquid formulation includes a yohimbine extract, a dissolution enhancer, and a solvent. Here, the dissolution ability of the yohimbine extract in the dissolution enhancer is higher than the dissolution ability of the yohimbine extract in the solvent, and the yohimbine extract can form a stable and transparent solution with the solvent after being dissolved in the dissolution enhancer. The amount of the yohimbine extract used in the aerosol generating system is improved by dissolving the yohimbine extract in the dissolution enhancer and then mixing it with the solvent of the liquid formulation, and the application of the yohimbine extract in the aerosol generating system is promoted.

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application claims priority to the Chinese patent application filed with the Chinese National Patent Office on October 26, 2021, application number 202111248947.0, with the title of invention "Liquid formulation and method for preparing the same, aerosol generating system, cylinder for aerosol generating system and aerosol generating apparatus," all of which are incorporated into this application by reference.

[0002] This application relates to the technical field of atomization, and more particularly to liquid formulations containing yohimbine, methods for preparing liquid formulations, aerosol generating systems, cylinders for aerosol generating systems, and aerosol generating devices. [Background technology]

[0003] An aerosol generation system includes an aerosol generator and a liquid formulation stored inside the aerosol generator. The aerosol generator forms an aerosol by atomizing the liquid formulation. The liquid formulation mainly includes glycerin, 1,2-propanediol, synthetic essences, nicotine and / or nicotine salts. In addition to being used as a substitute for conventional combustible cigarette products, aerosol generation systems may also be used for supplemental therapy. The main method involves adding health-beneficial ingredients to the liquid formulation, which then atomize to form an aerosol that is inhaled by the user. In recent years, the health industry has developed rapidly, and liquid formulations containing health-beneficial ingredients are attracting increasing attention from researchers, developers, and consumers. In particular, there is a focus on selecting health-beneficial ingredients that are truly beneficial to the user and adding them to the liquid formulation to exert the effects of those health-beneficial ingredients.

[0004] Yohimbe is a herbaceous plant that has been cultivated in Africa for over a hundred years, and many health products containing yohimbine extract are currently on the market. In conventional technology, yohimbine extract usually exists in the form of yohimbine hydrochloride. However, yohimbine hydrochloride has low solubility in glycerin-propanediol-based liquid formulations, is extremely prone to precipitation, and forms a cloudy liquid. This makes it difficult for yohimbine to be converted into an aerosol and inhaled by the user, significantly hindering the use of yohimbine extract in aerosol generating systems. [Overview of the Initiative]

[0005] To address the problem in the prior art of poor conversion of yohimbine components in liquid formulations containing yohimbine, the embodiments of this application provide a liquid formulation for an aerosol generating system comprising a yohimbine extract, a dissolution accelerator, and a solvent, wherein the solubility of the yohimbine extract in the dissolution accelerator is higher than the solvent's solvent capacity, and the yohimbine extract, after dissolving in the dissolution accelerator, can form a stable, clear solution with the solvent.

[0006] In some examples, the mass percentage content of the liquid formulation is 0.01 to 15% of the yohimbine extract, 0.09 to 15% of the dissolution accelerator, and 50 to 99.9% of the solvent.

[0007] In some embodiments, the yohimbine extract contains yohimbine.

[0008] In some embodiments, the yohimbine and the dissolution accelerator form a yohimbine concentrate, and the mass percentage content of the yohimbine concentrate is 0.1 to 30% by weight of the liquid formulation.

[0009] In some examples, the solvent comprises glycerin and propanediol.

[0010] In some examples, the mass percentage content of the yohimbine extract in the liquid formulation is 0.015 to 12% by weight, or 0.02 to 12% by mass.

[0011] In some examples, the dissolution accelerator comprises at least one of benzyl alcohol and an organic acid.

[0012] In some embodiments, the dissolution accelerator further contains water.

[0013] In some examples, the organic acid comprises at least one of lactic acid, glacial acetic acid, adipic acid, fumaric acid, tartaric acid, malic acid, citric acid, and benzoic acid.

[0014] In some examples, the mass percentage content of the benzyl alcohol in the liquid formulation is 0-27% by weight, or 0.008-15%, or 0.012-9% by weight.

[0015] In some examples, the mass percentage content of the organic acid in the liquid formulation is 0-24% by weight, or 0.008-15%, or 0.012-9% by weight.

[0016] In some examples, the mass percentage content of water in the liquid formulation is 0-24% by weight, or 0.01-15%, or 0.02-12% by weight.

[0017] In some embodiments, the liquid formulation further comprises at least one of a sweetener, a cooling agent, and a flavor composition.

[0018] The embodiments of the present application further provide a method for preparing the above liquid preparation, including the steps of preparing yohimbine, adding yohimbine to a dissolution promoter to fully dissolve yohimbine in the dissolution promoter to obtain a yohimbine concentrate, and adding the yohimbine concentrate to a solvent.

[0019] In some embodiments, the yohimbine is prepared by an oxidation treatment process of yohimbine hydrochloride.

[0020] The present application further provides a cartridge for an aerosol generating system containing the above liquid preparation.

[0021] The present application further provides an aerosol generating system including the above cartridge and an aerosol generating device, wherein the aerosol generating device is configured to receive at least a part of the cartridge and to be used for atomizing the liquid preparation to form an aerosol.

[0022] The embodiments of the present application further provide an aerosol generating device including an atomizer for atomizing the above liquid preparation to generate an aerosol and a cavity containing the above liquid preparation.

[0023] The beneficial effect of the embodiments of the present application is that in the above liquid preparation, the yohimbine extract is dissolved in the dissolution promoter, and the dissolution ability of the yohimbine extract in the dissolution promoter is higher than that in the solvent. Therefore, after the yohimbine extract is dissolved in the dissolution promoter, a stable transparent solution can be formed with the solvent in the liquid preparation, thereby improving the usage amount of the yohimbine extract in the aerosol generating system and promoting the application of the yohimbine extract in the aerosol generating system.

Brief Description of the Drawings

[0024] One or more embodiments will be exemplarily described by the figures in the corresponding attached drawings, but these exemplary descriptions do not limit the embodiments. Unless otherwise specified, the figures in the attached drawings do not limit the proportion. [Figure 1] The HPLC spectrum diagrams of yohimbine hydrochloride (a) and yohimbine sodium carbonate (b) before and after the deacidification process treatment provided in the examples of this application. [Figure 2] The HPLC spectrum diagram of the aerosol formed by atomizing yohimbine hydrochloride and yohimbine sodium carbonate provided in the examples of this application. [Figure 3] The comparison diagram of the dissolution status of three sets of solutions of liquid preparation a, liquid preparation b, and liquid preparation c provided in the examples of this application. [Figure 4] The comparison diagram of the conversion rates of four sets of yohimbine provided in Example 11 of this application.

Mode for Carrying Out the Invention

[0025] To make this application easier to understand, the drawings and specific embodiments will be combined below to describe this application in more detail.

[0026] The yohimbine extract is an active substance extracted from the bark of the natural plant "YOHIMBE" yohimbine that grows in Africa. Yohimbine can act on the reproductive organs, dilate the blood vessels of the reproductive organs, increase the blood flow volume of the reproductive organs, and enhance sexual function by increasing the formation of nitrous oxide. This is a pure plant preparation for treating erectile dysfunction with plants that is currently affirmative and most widely applied, and it can also prevent prostate hypertrophy and urinary system infections. In addition to adding the yohimbine extract to the liquid preparation used in the aerosol generation system, it is atomized by an aerosol generator to form an aerosol. By inhaling the aerosol, the user can make yohimbine exert its functional effects. Therefore, applying yohimbine to the field of the aerosol generation system can greatly expand the health use effect of the aerosol generator.

[0027] Yohimbine extract contains yohimbine hydrochloride and yohimbine. Yohimbine has the chemical formula C21H26N2O3, is readily soluble in chloroform, soluble in methanol and ethanol, and slightly soluble in water. Commercially available yohimbine extracts mainly exist in the form of yohimbine hydrochloride. Yohimbine hydrochloride has the chemical formula C21H27CLN2O3, is readily soluble in chloroform, soluble in methanol and ethanol, and slightly soluble in water. Through testing, it was found that both yohimbine hydrochloride and yohimbine have extremely low solubility in glycerin and propanediol-based solvents, and that crystals precipitate when the amount of yohimbine hydrochloride and yohimbine added is far below 1% by weight in a liquid formulation. Because yohimbine extract is poorly soluble in solvents, it is difficult for yohimbine to be converted into an aerosol and inhaled by the user.

[0028] To facilitate the effective application of yohimbine extract in aerosol generating systems, Example 1 of this application provides a liquid formulation containing yohimbine extract for use in an aerosol generating system. The liquid formulation comprises a solvent and a yohimbine concentrate. The yohimbine extract is present in the yohimbine concentrate. The yohimbine concentrate can form a stable, clear solution with a glycerin-propanediol solvent, thereby solving the problem of yohimbine extract being poorly soluble in glycerin-propanediol solvents.

[0029] In the weight percentage of the liquid formulation, the mass percentage content of yohimbine concentrate is 0.1 to 30%, and the mass percentage content of the solvent is 50 to 99.9%. The yohimbine concentrate contains yohimbine extract. In the weight of the liquid formulation, the mass percentage content of yohimbine extract is 0.01 to 15%, or 0.015 to 12%, or 0.02 to 12%.

[0030] Furthermore, in the yohimbine concentrate, the mass percentage of yohimbine extract may be 10-50% by weight of the yohimbine concentrate, selectively 15-40%, and even more precisely 20-40%. Therefore, the mass percentage of yohimbine extract may be 0.01-15% by weight of the liquid formulation, selectively 0.015-12%, and even more precisely 0.02-12%. The specific amount of yohimbine extract added selectively can be adjusted according to the user's needs. For example, the mass percentage of yohimbine extract by weight of the liquid formulation may be 1%, 2%, 5%, 6%, 8%, 10%, 12%, 14%, or any value between 0.01-15%. Since yohimbine extract can be dissolved in large quantities with a dissolution accelerator to form a yohimbine concentrate, the amount of yohimbine extract added to a liquid formulation can be arbitrarily changed by adjusting the mixing ratio of the yohimbine concentrate in the liquid formulation.

[0031] Implementation 1 of this application further provides a part of a specific component formulation for preparing the above-mentioned liquid formulation. The mass percentage content of each component in the total volume percentage of the liquid formulation is shown in Table 1 below.

[0032] JPEG0007830634000001.jpg36164

[0033] The yohimbine extract is present in the yohimbine concentrate mainly in the form of yohimbine. In some embodiments, the solvent mainly comprises glycerin and propanediol, and the two components, glycerin and propanediol, can be mixed in any proportion. In selective embodiments, the solvent may further contain one or more of butanediol, 1,2,4-butanetriol, dipropylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol 200, polyethylene glycol 400, glycerol triacetate, dipropylene glycol ether, ethanol, water, triethyl citrate, and tri(caprylic / capric acid)glyceryl. The specific selection of the solvent needs to be optimized depending on the types of components added to the solvent. Glycerin and propanediol are preferred components in the solvent from the viewpoint of improving the quality of the aerosol generated by the aerosol generator.

[0034] Due to the limited supply of yohimbine, in Example 2 provided in this application, yohimbine is formed by a deacidification process of yohimbine hydrochloride. The deacidification process of organic matter can be carried out by oxidation or acid-base neutralization, where the acid-base neutralization method includes an esterification reaction. Hereinafter, the esterification reaction will be described in detail as an example, and the deacidification process of yohimbine hydrochloride mainly includes the following steps.

[0035] Step 1: Esterification reaction Add yohimbine hydrochloride powder to ethyl acetate and dissolve thoroughly. Transfer to a separatory funnel, add distilled water, shake the funnel vigorously to mix uniformly, and allow to stand until layered. Here, the ratio of yohimbine hydrochloride to ethyl acetate is 1:(40-70) by weight, and the ratio of distilled water to ethyl acetate is 1:(2-3) by volume.

[0036] Step 2: pH adjustment and filtration After the solution has separated, an aqueous layer and an ethyl acetate layer are formed, with the upper layer being the ethyl acetate layer and the lower layer being the aqueous layer. A sufficient amount of sodium hydroxide solution is added, the separatory funnel is shaken vigorously, and the mixture is stopped until its pH reaches approximately 9. After standing until the mixture separates, the lower water layer is drained.

[0037] Add enough pure water again to wash the upper ethyl acetate layer, and repeat this process three times. Here, the concentration of the sodium hydroxide solution is 2-6 mol / L, and when calculated by volume ratio, the ratio of pure water to ethyl acetate is 1:(2-3).

[0038] Step 3: Purification of yohimbine The ethyl acetate layer from the above step is collected, the mixture is placed in a rotary evaporator, and the liquid in the rotary bottle is evaporated under reduced pressure until it turns into a dry solid. The powdered solid is then removed to obtain yohimbine.

[0039] By repeating the third step to purify the powder, yohimbine powder with a purity of 98% (by mass percentage) or higher can be obtained.

[0040] In Example 3 provided in this application, the effect of the deoxidation process in Example 2 on the active ingredient of yohimbine is analyzed by detection comparison. The detection analysis method involves adding yohimbine hydrochloride before the deoxidation process and yohimbine after the deoxidation process to a liquid chromatograph and verifying whether the deoxidation process affects the active ingredient of yohimbine by comparative analysis of liquid chromatography. The comparative analysis method of liquid chromatography will be described in detail below.

[0041] (1) The chromatography conditions were as follows: DGU-20A5R liquid chromatograph, reversed-phase chromatography column C18, 4.6 x 250 mm, 3.5 μm, mobile phase acetonitrile monohydrate (volume ratio 30:70), column temperature 35°C, flow rate 1.0 mL / min, detection wavelength 278 nm, sample size 10 μL.

[0042] (2) Yohimbine hydrochloride and yohimbine obtained in the deacidification process are added to a chromatograph, and spectral analysis is performed using liquid chromatography. Comparative analysis of the liquid chromatography results in the obtained chromatograms (see Figure 1), and the peak intervals of the two chromatograms are identical. This chromatographic analysis clearly shows that the deacidification process provided in Example 2 of this application does not affect the active functional groups of yohimbine.

[0043] In Example 4 provided in this application, yohimbine hydrochloride before the deoxidation process is further prepared as an atomized liquid formulation 1, and yohimbine after the deoxidation process is prepared as an atomized liquid formulation 2. Liquid formulation 1 is added to an aerosol generator and atomized to obtain aerosol 1, and liquid formulation 2 is added to an aerosol generator and atomized to obtain aerosol 2. Then, a comparative analysis of the performance of aerosol 1 and aerosol 2 is performed using liquid chromatography. The specific comparative analysis method using liquid chromatography is the same as for solution 1 and solution 2 described above, and can be found in the following description.

[0044] (1) The chromatography conditions were as follows: DGU-20A5R liquid chromatograph, reversed-phase chromatography column C18, 4.6 x 250 mm, 3.5 μm, mobile phase acetonitrile monohydrate (volume ratio 30:70), column temperature 35°C, flow rate 1.0 mL / min, detection wavelength 278 nm, sample size 10 μL.

[0045] (2) Aerosol 1 and Aerosol 2 were each collected and placed in a liquid chromatograph for liquid chromatography analysis. Comparative analysis of the liquid chromatography results in the obtained chromatograms, which can be seen in Figure 2. The peak intervals of the two chromatograms are substantially identical, and the peak intervals of Figure 2 and Figure 1 are also substantially identical. The above chromatographic analysis revealed that Aerosol 1 contains the yohimbine component, Aerosol 2 contains the yohimbine component, and that both yohimbine hydrochloride and yohimbine can be absorbed into the human body in aerosol form and achieve health benefits. It should be explained that since neither liquid formulation 1 nor liquid formulation 2 uses a glycerin-propanediol-based solvent system, both yohimbine hydrochloride and yohimbine can be effectively converted into aerosols.

[0046] To maximize the solubility of yohimbine in propanediol-glycerin solvents, the yohimbine obtained through the above deoxidation process is prepared as a yohimbine concentrate. Example 5 of this application provides a formulation for the yohimbine concentrate. The yohimbine concentrate contains yohimbine and a dissolution accelerator, and the yohimbine is sufficiently soluble in the dissolution accelerator, forming a stable, clear solution without the formation of yohimbine precipitates. The dissolution accelerator includes benzyl alcohol, an organic acid, and water. Benzyl alcohol and the organic acid are suitable components as dissolution accelerators. The organic acid includes, but is not limited to, one or more combinations of lactic acid, glacial acetic acid, adipic acid, fumaric acid, malic acid, citric acid, and benzoic acid. Among the organic acids, lactic acid and glacial acetic acid are preferred. Regarding the mechanism of yohimbine dissolution in dissolution accelerators, on the one hand, yohimbine can form intermolecular hydrogen bonds with benzyl alcohol or organic acids, thereby promoting its dissolution in benzyl alcohol or organic acid solvents. On the other hand, since yohimbine is a polar organic substance, and benzyl alcohol, glacial acetic acid, and lactic acid are polar organic solvents, they can promote the dissolution of yohimbine in these two types of substances. The polarity of propanediol and glycerin is lower than that of benzyl alcohol, glacial acetic acid, and water, and according to the principle that like dissolves like, polar yohimbine dissolves more easily in dissolution accelerators formed by mixing highly polar benzyl alcohol, glacial acetic acid, lactic acid, and water.

[0047] In the yohimbine concentrate, the mass percentage of yohimbine is 10-50% by weight, selectively 15-40%, and furthermore 20-40%. In the yohimbine concentrate, the mass percentage of benzyl alcohol is 0-90% by weight, selectively 8-50%, and furthermore 12-30%. In the yohimbine concentrate, the mass percentage of organic acids is 0-80% by weight, selectively 8-50%, and furthermore 12-30%. In the yohimbine concentrate, the mass percentage of water is 0-80% by weight of the yohimbine concentrate, selectively 10-50%, and even more preferably 20-40%. As understood, the dissolution accelerator may be selected from any organic substance capable of promoting the dissolution of yohimbine or yohimbine hydrochloride, but it must satisfy the atomization function requirements of the atomized liquid formulation of the aerosol generating system, be able to form an aerosol suitable for inhalation, and not affect the performance of the aerosol formed by atomizing the liquid formulation, which includes texture, smoke stability, and user health.

[0048] In the liquid formulation, the mass percentage of benzyl alcohol is 0-27% by weight of the liquid formulation, selectively 0.008-15%, and selectively 0.012-9%. As can be understood, the specific amount of benzyl alcohol added can be adaptively adjusted according to the amount of yohimbine that needs to be dissolved, and the mass percentage content of benzyl alcohol can be any value between 0-27%.

[0049] In the liquid formulation, the mass percentage content of organic acids is 0-24% by weight of the liquid formulation, selectively 0.008-15%, and selectively 0.012-9%. As can be understood, the specific amount of organic acid added can be adaptively adjusted according to the amount of yohimbine that needs to be dissolved, and the mass percentage content of organic acids can be any value between 0-24%.

[0050] The specific content of the dissolution accelerator in the yohimbine concentrate is not limited to the above content range and can be adaptively adjusted according to the required content of yohimbine extract. For example, if the required content of yohimbine extract in a liquid formulation for an aerosol production system is 3% (by mass percentage), and the content of the yohimbine concentrate in the liquid formulation is 15% (by mass percentage), then the yohimbine concentrate will contain 20% (by mass percentage) of yohimbine extract and 80% (by mass percentage) of the dissolution accelerator.

[0051] Example 6 of this application further provides a process for preparing the yohimbine concentrate, which includes the following steps.

[0052] 1. Weigh the yohimbine powder and add benzyl alcohol solvent so that the benzyl alcohol can thoroughly soak the yohimbine powder.

[0053] 2. By adding pure water, the yohimbine powder in the above solution can be further impregnated.

[0054] 3. Add glacial acetic acid to the above solution.

[0055] 4. Seal the container holding the above solution, heat it to 60°C, and stir or swirl it to thoroughly dissolve the yohimbine powder in the solution.

[0056] 5. Filter out impurities from the above solution to obtain a concentrated yohimbine solution.

[0057] It should be explained that during the preparation of yohimbine concentrate, the content of each component differs, the solubility of the corresponding yohimbine powder varies, and although the purity of the yohimbine used is greater than 98%, it still contains small amounts of impurities. In some formulations, yohimbine is completely dissolved in the yohimbine concentrate, while in others, the yohimbine is not completely dissolved. In this case, there are trace amounts of suspended matter or undissolved crystal nuclei in the concentrate. To obtain a stable yohimbine concentrate, it is necessary to select the number of operations in step 5 according to the condition of the prepared concentrate and thoroughly filter out the impurities from the prepared yohimbine concentrate.

[0058] Furthermore, Example 5 of this application further provides a part of a specific ingredient formulation for preparing the above-mentioned yohimbine concentrate. See Table 2 below.

[0059] JPEG0007830634000002.jpg60164

[0060] It should be noted that Table 1 only describes a portion of the formulations for preparing yohimbine concentrate, and that while the proportions of the mass content of each component provided in the examples of this application are met, the formulations can be adaptively adjusted according to specific yohimbine extract concentration needs.

[0061] In Example 7 of this application, a comparative analysis of the solubility of atomized solutions obtained by adding different yohimbine extracts to a glycerin-propanediol solvent is performed. The specific analytical method is as follows.

[0062] (1) Prepare liquid formulation a: Add yohimbine hydrochloride to a glycerin-propanediol solvent, where the mass ratio content of yohimbine hydrochloride is 2% by weight of liquid formulation a, and heat liquid formulation a for 30 minutes at a heating temperature of 60°C.

[0063] (2) Prepare liquid formulation b: Add the yohimbine obtained in the deoxidation process of Example 2 above to a glycerin-propanediol solvent, where the mass ratio content of yohimbine is 2% by weight of liquid formulation b, and heat liquid formulation b for 30 minutes at a heating temperature of 60°C.

[0064] (3) Prepare liquid formulation c: Add the yohimbine concentrate provided in Example 5 of this application to a glycerin-propanediol solvent, where the mass percentage content of yohimbine is 2% by weight of liquid formulation c, and heat liquid formulation c for 30 minutes at a heating temperature of 60°C.

[0065] The dissolution status of three sets of solutions—liquid formulation a, liquid formulation b, and liquid formulation c—was observed. Refer to Table 2 and Figure 3 for the dissolution status of the three sets of solutions obtained.

[0066] JPEG0007830634000003.jpg17164

[0067] Referring to Table 3 and Figure 3, the solutions of liquid formulations a and b were cloudy, indicating that the solubility of yohimbine hydrochloride in the glycerin-propanediol solvent was low, and that the solubility of yohimbine prepared through a deacidification process in the glycerin-propanediol solvent was also low. However, the solution of liquid formulation c was clear and transparent, and even after being left to stand for a certain period of time and observed, the solution c remained transparent without any crystal precipitation. Thus, it was clear that the yohimbine concentrate provided in Example 5 of this application can form a stable, transparent solution system in the glycerin-propanediol solvent. By preparing yohimbine as a yohimbine concentrate, the problem of addition in its liquid formulations can be solved, the amount of yohimbine extract added can be increased according to specific usage needs, and the prepared atomized liquid formulation is highly stable and does not precipitate.

[0068] Example 9 of this application further conducts a comparative analysis of the conversion effect of yohimbine in which liquid formulations containing different yohimbine extracts are converted into aerosols in an aerosol generator. Two sets of liquid formulations containing yohimbine extract are prepared, designated as liquid formulation 3 and liquid formulation 4. Liquid formulation 3 is atomized in an aerosol generator to form aerosol 3, and liquid formulation 4 is atomized in an aerosol generator to form aerosol 4.

[0069] Liquid formulation 3 is prepared by adding yohimbine hydrochloride to a glycerin-propanediol solvent, and when calculated by weight percentage of liquid formulation 3, the mass percentage of yohimbine hydrochloride is 1%, the mass percentage of propanediol is 49%, and the mass percentage of glycerin is 50%.

[0070] Liquid formulation 4 is prepared by adding yohimbine concentrate to a glycerin-propanediol solvent. Calculated by weight percentage, liquid formulation 4 contains 30% yohimbine concentrate, 20% propanediol, and 50% glycerin. In liquid formulation 4, the yohimbine concentrate contains 3.33% by weight, and calculations show that the yohimbine concentrate in liquid formulation 4 contains 1% by weight.

[0071] Embodiment 10 of this application provides an aerosol generator for an aerosol generation system, including an atomizer having an atomizing function. The atomizer includes a heating element and a fluid guide element. The fluid guide element can absorb and transfer a liquid formulation, and the heating element can atomize the liquid formulation to form an aerosol. Depending on the material used in the fluid guide element and the manufacturing process of the atomizer, the atomizer includes a ceramic core atomizer and a cotton core atomizer. In a cotton core atomizer, the fluid guide element can be manufactured from a material having a capillary structure and excellent liquid storage performance, such as nonwoven fabric or cotton. The heating element may be a spiral heating wire or heating mesh manufactured from at least one of the following materials: stainless steel, nickel-chromium alloy, iron-chromium-aluminum alloy, metallic titanium, etc. The fluid guide element may be fixedly provided on the outside of the spiral heating wire or heating mesh, or the spiral heating wire or heating mesh may be provided around at least a portion of the surface of the fluid guide element. In a ceramic core atomizer, the fluid guide element may be a porous structure made of a hard capillary structure such as porous ceramic, porous glass ceramic, or porous glass, and the fluid guide element is substantially block-shaped, with a heating element fixed to at least a portion of its surface. The heating element may be one of a heating coating, a heating sheet, or a heating mesh. Here, the heating coating may include, but is not limited to, electromagnetic induction heating paint and infrared induction heating paint. Alternatively, the heating element can be made by using conductive raw material powder, mixing it with a printing aid to make a slurry, and then sintering it onto the porous surface after printing. In Example 9 of this application, a comparative analysis of the effects of a ceramic atomizer and a cotton core atomizer on the conversion rate of yohimbine in a liquid formulation is performed.

[0072] In Example 9 of this application, the conversion rate of yohimbine in aerosol 3 and aerosol 4 is tested and analyzed, and the test method used is described below.

[0073] The test method includes the step of performing an inhalation test using a smoker for each of liquid formulations 3 and 4 in accordance with international standards. The specific inhalation test conditions are that each inhalation time is 3 seconds, the inhalation time interval is 30 seconds, the number of inhalations is 50, and the amount of liquid formulation inhaled each time is 55 mL. Aerosol 3 and aerosol 4 are collected using a Cambridge filter. Yohimbine hydrochloride from aerosol 3 is extracted using an organic solvent and filtered to obtain yohimbine hydrochloride, while yohimbine from aerosol 4 is extracted using an organic solvent and filtered to obtain yohimbine. Using liquid chromatography analysis, the conversion rate of yohimbine hydrochloride in aerosol 3, formed by atomizing yohimbine hydrochloride in liquid formulation 3, and the conversion rate of yohimbine in aerosol 4, formed by atomizing yohimbine in liquid formulation 4, are calculated according to the following conversion rate calculation formula.

[0074] The formula for calculating the conversion rate is: The image is JPEG0007830634000004.jpg1043, and in the formula, C0 = m0 / V and C1 = m1 / V.

[0075] In the above conversion rate calculation formula, W% is the conversion efficiency of yohimbine, C0 is the concentration of the aerosol collected by the Cambridge filter, C1 is the concentration of the liquid formulation, A0 is the chromatogram peak area of ​​yohimbine in the aerosol, A1 is the chromatogram peak area of ​​yohimbine in the liquid formulation, m0 is the mass of the aerosol (i.e., the mass difference before and after collection by the Cambridge filter), m1 is the mass of the liquid formulation, and V is the volume of the extraction solvent.

[0076] In Example 9 provided in this application, liquid formulation 3 is added to aerosol generator 1 of the same specifications equipped with a cotton core atomizer and aerosol generator 2 of the same specifications equipped with a ceramic atomizer, respectively. Liquid formulation 4 is then added to aerosol generator 3 of the same specifications equipped with a cotton core atomizer and aerosol generator 4 of the same specifications equipped with a ceramic atomizer, respectively. Subsequently, aerosol generators 1, 2, 3, and 4 are each connected to the same smoking device, and a first set of aerosols, a second set of aerosols, a third set of aerosols, and a fourth set of aerosols are obtained according to the inhalation test method described above. Subsequently, sample 1 of yohimbine hydrochloride from the first aerosol was extracted using the same organic solvent, sample 2 of yohimbine hydrochloride from the second aerosol was extracted using the same organic solvent, sample 3 of yohimbine from the third aerosol was extracted using the same organic solvent, and sample 4 of yohimbine from the fourth aerosol was extracted using the same organic solvent. Then, samples 1, 2, 3, and 4 were each added to a liquid chromatography analyzer, and liquid chromatography analysis was performed to determine that the chromatogram peak area of ​​yohimbine in sample 1 was A 01 Therefore, the chromatogram peak area of ​​yohimbine in sample 2 is A 02 Therefore, the chromatogram peak area of ​​yohimbine in sample 3 is A 03 Furthermore, the chromatogram peak area of ​​yohimbine in sample 4 is A 04 It can be seen that this is the case.

[0077] Prepare liquid formulation 3 and liquid formulation 4, where the mass of liquid formulation 3 is m 13 The mass of liquid formulation 4 is m 14 The above liquid formulations 3 and 4 were each placed in a liquid chromatograph and analyzed using liquid chromatography, and the chromatogram peak area corresponding to yohimbine in liquid formulation 3 was A 13 Therefore, the chromatogram peak area corresponding to yohimbine in liquid formulation 4 is A 14 It can be seen that this is the case.

[0078] After that, A 01 and A 13 are substituted into the above conversion rate calculation formula, and the conversion efficiency of yohimbine hydrochloride in the first set of aerosols formed by atomizing the yohimbine hydrochloride liquid preparation in the aerosol generator 1 equipped with a cotton core atomizer is obtained. A 02 and A 13 are substituted into the above conversion rate calculation formula, and the conversion efficiency of yohimbine hydrochloride in the second set of aerosols formed by atomizing the yohimbine hydrochloride liquid preparation in the aerosol generator 2 equipped with a ceramic core atomizer is obtained. A 03 and A 14 are substituted into the above conversion rate calculation formula, and the conversion efficiency of yohimbine in the third set of aerosols formed by atomizing the yohimbine concentrated liquid preparation in the aerosol generator 3 equipped with a cotton core atomizer is obtained. A 04 and A 14 are substituted into the above conversion rate calculation formula, and the conversion efficiency of yohimbine in the fourth set of aerosols formed by atomizing the yohimbine concentrated liquid preparation in the aerosol generator 4 equipped with a ceramic core atomizer is obtained.

[0079] Finally, the results of the four sets of analytical comparative tests are shown in Figure 4. As can be seen from the figure, in the aerosol generator equipped with a ceramic core, corresponding to atomizer 1 in Figure 4, the conversion rate of yohimbine in the aerosol formed by atomizing the yohimbine hydrochloride liquid formulation was 51%, and in the aerosol formed by atomizing the yohimbine concentrate liquid formulation, the conversion rate of yohimbine was 81%. In other words, using the liquid formulation prepared by the yohimbine concentration process provided in the embodiments of this application can significantly improve the yohimbine content in the aerosol. In an aerosol generator equipped with a cotton core, corresponding to atomizer 2 in Figure 4, the conversion rate of yohimbine in the aerosol formed by atomizing a yohimbine hydrochloride liquid formulation is 36%, and the conversion rate of yohimbine in the aerosol formed by atomizing a yohimbine concentrate liquid formulation is 56%. In other words, using a liquid formulation prepared by the yohimbine concentration process provided in the embodiments of this application can significantly improve the yohimbine content in the aerosol. In a similarly yohimbine-containing liquid formulation, the yohimbine content in the aerosol formed by atomizing using an aerosol generator equipped with a ceramic atomizer is N1, and the yohimbine content in the aerosol formed by atomizing using an aerosol generator equipped with a cotton core atomizer is N2, where N1 > N2. Therefore, an aerosol generator equipped with a ceramic core atomizer has a higher atomizing effect on yohimbine-containing liquid formulations and can improve the conversion rate of yohimbine.

[0080] Example 11 of this application further provides a liquid formulation containing yohimbine for use in an aerosol generating system. The liquid formulation comprises a yohimbine concentrate, a solvent, a sweetener, a cooling agent, and a flavor composition. By weight of the liquid formulation, the mass percentage content of the yohimbine concentrate is 0.1 to 30%, the mass percentage content of the solvent is 50 to 99.9%, the mass percentage content of the sweetener is 0.01 to 0.5%, the mass percentage content of the cooling agent is 0.01 to 8%, and the mass percentage content of the flavor composition is 0.01 to 15%.

[0081] The liquid formulations provided in Example 11 of this application include, but are not limited to, a combination of one or more of the following solvents: propanediol, glycerin, butanediol, 1,2,4-butanetriol, dipropylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol 200, polyethylene glycol 400, glycerol triacetate, dipropylene glycol ether, ethanol, water, triethyl citrate, and tri(caprylic / capric acid)glyceryl.

[0082] The liquid formulation provided in Example 11 of this application contains, but is not limited to, one or more combinations of menthol, menthone, isomentone, WS-23 (2-isopropyl-N,2,3-trimethylbutylamide), WS-3 (N-ethyl-p-menthane-3-carboxamide), WS-5 (N-(ethoxycarbonylmethyl)-p-menthane-3-carboxamide), menthyl lactate, and menthol glycerin acetal, with a total addition amount of 0.01% to 8% (by mass percentage).

[0083] The liquid formulation provided in Example 11 of this application contains, but is not limited to, a combination of one or more of the following sweeteners: neotame, cyclamate, sucralose, aspartame, stevioside, and acesulfame potassium, with a total addition amount of 0.01 to 0.5% (by mass percentage).

[0084] In the liquid formulation provided in Example 11 of this application, the flavor composition is a natural or synthetic essence flavoring and includes, but is not limited to, flavors such as fruit, floral, tea, mint, coffee, cider, candy, or tobacco. The addition of the flavor composition can be used to enrich the texture of the aerosol formed by atomizing the liquid formulation.

[0085] Embodiment 12 of this application further provides an aerosol generator. The aerosol generator comprises a cylinder capable of containing a liquid formulation provided in any one embodiment of this application, the liquid formulation containing a yohimbine extract. Inside the aerosol generator are an atomizer capable of atomizing the liquid formulation to form an aerosol, and a control module that enables the stable release of the aerosol, the atomizer being powered to atomize and to deliver the aerosol to the outside of the aerosol generator via an aerosol delivery passage within the aerosol generator for the user to inhale. In addition to electrically driven atomization, the aerosol generator can also atomize the liquid formulation in other ways to form an aerosol and effectively deliver it to the user, the optimal selection of which can be made based on the atomization temperature of the specific components of the liquid substrate in the cylinder of the aerosol generator, and the specific atomization method is not limited. In some embodiments, the aerosol generator can atomize using a resistive and / or electromagnetic heating element, in other embodiments, ultrasonic atomization may be performed, or electric heating atomization and ultrasonic atomization may be performed simultaneously, and in some embodiments, the aerosol generator may be an air compression atomizer or a pressure sprayer.

[0086] It should be noted that while the specification and drawings of this application illustrate preferred embodiments of this application, they are not limited to those embodiments described herein, and furthermore, those skilled in the art can improve or modify based on the above description, all such improvements and modifications should fall within the scope of protection of the claims attached to this application.

Claims

1. It contains yohimbine extract, a dissolution accelerator, and a solvent. A liquid formulation for an aerosol generating system, wherein the solubility of the yohimbine extract in the dissolution accelerator is higher than the solubility of the yohimbine extract in the solvent, and the dissolution accelerator comprises at least one of benzyl alcohol and an organic acid.

2. The liquid formulation according to claim 1, wherein, by mass percentage of the liquid formulation, the mass percentage content of the yohimbine extract is 0.01 to 15%, the mass percentage content of the dissolution accelerator is 0.09 to 15%, and the mass percentage content of the solvent is 50 to 99.9%.

3. The liquid formulation according to claim 1, wherein the yohimbine extract contains yohimbine.

4. The yohimbine extract and the dissolution accelerator form a yohimbine concentrate. The liquid formulation according to claim 1, wherein the mass percentage content of the yohimbine concentrate in the weight percentage of the liquid formulation is 0.1 to 30%.

5. The liquid formulation according to claim 1, wherein the solvent comprises glycerin and propanediol.

6. The liquid formulation according to claim 3, wherein the mass percentage content of the yohimbine extract in the weight percentage of the liquid formulation is 0.015 to 12%, or the mass percentage content of the yohimbine extract is 0.02 to 12%.

7. The liquid formulation according to claim 1, wherein the dissolution accelerator further comprises water.

8. The liquid formulation according to claim 1, wherein the organic acid comprises at least one of lactic acid, glacial acetic acid, adipic acid, fumaric acid, tartaric acid, malic acid, citric acid, and benzoic acid.

9. The weight percentage content of the liquid formulation is 0-27% by mass, where the mass percentage content of benzyl alcohol is 0-27%. Alternatively, the mass percentage content of the benzyl alcohol is 0.008 to 15%. Alternatively, the liquid formulation according to claim 1, wherein the mass percentage content of the benzyl alcohol is 0.012 to 9%.

10. The weight percentage content of the aforementioned liquid formulation is 0 to 24% by mass, Alternatively, the mass percentage content of the organic acid is 0.008 to 15%. Alternatively, the liquid formulation according to claim 1, wherein the mass percentage content of the organic acid is 0.012 to 9%.

11. The weight percentage of the liquid formulation contains 0 to 24% of the mass percentage of water. Alternatively, the mass percentage content of the water is 0.01 to 15%. Alternatively, the liquid formulation according to claim 7, wherein the mass percentage content of water is 0.02 to 12%.

12. The liquid formulation according to claim 1, further comprising at least one of a sweetener, a cooling agent, and a flavor composition.

13. To prepare yohimbine, Adding yohimbine to a dissolution accelerator and thoroughly dissolving the yohimbine in the dissolution accelerator to obtain a concentrated yohimbine solution, A method for preparing a liquid formulation according to any one of claims 1 to 12, comprising adding yohimbine concentrate to a solvent.

14. The method for preparing a liquid formulation according to claim 13, wherein the yohimbine is prepared by a deacidification process with yohimbine hydrochloride.

15. A cylinder for an aerosol generating system, containing a liquid formulation comprising the liquid formulation according to any one of claims 1 to 12.

16. The cylinder and aerosol generator described in claim 15 are included, The aerosol generating device is an aerosol generating system that is capable of receiving at least a portion of the cylinder and is configured to be used to atomize the liquid formulation to form an aerosol.

17. An aerosol generator comprising an atomizer and a cavity containing a liquid formulation according to any one of claims 1 to 12, wherein the atomizer is used to atomize the liquid formulation and generate an aerosol.

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