Liquid formulations, cartridges, and aerosol generating systems usable for atomization by electronic atomizers.

Abstract

This application discloses a liquid formulation, a cartridge, and an aerosol generating system usable for atomization by an electronic atomizer, wherein the liquid formulation comprises a solvent and azelastine hydrochloride.

Description

Technical Field

[0006] ,

[0001] (Cross - reference to related applications) This application claims the priority of a Chinese patent application with the application number 202310351111.6 and the invention title "Liquid preparation, cartridge and aerosol generation system that can be used for atomization by an electronic atomizer", which was filed with the China National Intellectual Property Administration on March 29, 2023, and all of its contents are incorporated herein by reference.

[0002] Embodiments of this application relate to the field of aerosol generation devices, and in particular, to a liquid preparation, a cartridge, and an aerosol generation system that can be used for atomization by an electronic atomizer.

Background Art

[0003] Azelastine Hydrochloride (AH) is a potential long - acting anti - allergic compound with the properties of an H1 receptor antagonist, having anti - allergic, anti - asthmatic, and anti - histamine properties, and is usually used clinically for the treatment of allergic rhinitis and asthma.

[0004] Azelastine Hydrochloride used as a drug is prepared as tablets or granules for oral administration by patients, or as sprays for nasal spraying by patients, or as eye drops for eye dropping by patients.

[0005] Azelastine Hydrochloride used as tablets or granules has a strong bitter taste, while Azelastine Hydrochloride used as nasal sprays or eye drops is inconvenient to carry and cannot be used at any time for users to relieve discomfort.

Summary of the Invention

[0006] Embodiments of this application provide a solvent, and azelastine hydrochloride, and provide a liquid preparation that can be used for atomization by an electronic atomizer.

[0007] In the above embodiment, azelastine hydrochloride is prepared as a liquid formulation usable for atomization by an electronic atomizer, and this liquid formulation is added to the electronic atomizer and atomized to generate an aerosol for the user to inhale. On the one hand, all electronic atomizers currently used for atomizing and inhaling azelastine hydrochloride are designed to be portable, making them easy for users to carry, improving patient compliance, and enriching the range of applications in clinical treatment. On the other hand, although the boiling point of azelastine hydrochloride is approximately 534°C, the operating temperature range of current electronic atomizers is approximately 100°C to 500°C, so azelastine hydrochloride can undergo azeotrope with the common solvent in the electronic atomizer and generate an aerosol. Furthermore, when azelastine hydrochloride was prepared as a liquid formulation and atomization was measured using an electronic atomizer, it was found that azelastine hydrochloride has a high atomization conversion rate. Therefore, in the process of the user inhaling the aerosol generated by atomizing the above liquid formulation, azelastine hydrochloride can be inhaled into the lungs, reach the alveoli, be rapidly absorbed, and enter the bloodstream. Its biological efficacy is significantly higher than that of oral administration. Consequently, preparing azelastine hydrochloride as a liquid formulation and inhaling it via atomization allows for better efficacy.

[0008] The above-mentioned azelastine hydrochloride is a pharmaceutical-grade raw material and can be prepared by various methods reported in the prior art.

[0009] In some examples, the mass percentage of azelastine hydrochloride in the liquid formulation is 0.01% to 3%, or the mass percentage of azelastine hydrochloride in the liquid formulation is 0.1% to 1%.

[0010] When azelastine hydrochloride is used as a tablet, the daily dose for adults is limited to 4 mg or less. Based on the volume of smoke per puff of the electronic atomizer and the number of puffs inhaled by the user per day, the mass percentage content of azelastine hydrochloride is controlled to within 3%, allowing the user to alleviate unpleasant symptoms of rhinitis and asthma with multiple inhalations per day.

[0011] Furthermore, measurements of the atomization effect of liquid formulations of azelastine hydrochloride showed that when the mass percentage of azelastine hydrochloride in the liquid formulation is controlled to approximately 0.1% to 1%, the conversion rate from azelastine hydrochloride in the liquid formulation to an aerosol is almost always over 90%, and sometimes even approaches 100%. Therefore, controlling the mass percentage of azelastine hydrochloride in the liquid formulation to within 0.1% to 1% is advantageous for improving the conversion rate.

[0012] In some examples, the solvent comprises at least one of propylene glycol, vegetable glycerin, water, or ethanol.

[0013] In some examples, the mass percentage of propylene glycol in the liquid formulation is 20% to 80%.

[0014] In some examples, the mass percentage of the plant glycerin in the liquid formulation is 30% to 70%.

[0015] The propylene glycol mentioned above can be selected as either 1,2-propylene glycol or 1,3-propylene glycol.

[0016] Propylene glycol and vegetable glycerin are commonly used solvents in electronic atomizers, exhibiting excellent performance in increasing vapor volume and controlling the fluidity of liquid formulations. Therefore, by using propylene glycol and vegetable glycerin as the main solvent components, and simultaneously adding an appropriate amount of water or ethanol as a solvent in proportion to the increase in the mass percentage content of azelastine hydrochloride in the liquid formulation, the solubility of azelastine hydrochloride in the liquid formulation can be increased.

[0017] In some examples, the atomization conversion rate of azelastine hydrochloride is 90% or more, or 80% or more, or 70% or more, or 60% or more.

[0018] In some examples, the particle size range of the aerosol generated when azelastine hydrochloride in a liquid formulation usable for atomization by the aforementioned electronic atomizer is atomized by the electronic atomizer is 0.2 μm to 3 μm.

[0019] Most of the aerosol particles of the above-mentioned azelastine hydrochloride are concentrated in the range of 0.2 μm to 1.5 μm.

[0020] Measurements using the atomization measurement method provided in the embodiments of this application show that the atomization conversion rate of a liquid formulation in which azelastine hydrochloride is present within a certain content range is 90% or higher, and this content is generally set to 0.1% to 1% (mass percentage). When the content of azelastine hydrochloride in the liquid formulation is adjusted to a certain range, the conversion rate of azelastine hydrochloride is 80% or higher. Furthermore, when the content of azelastine hydrochloride in the liquid formulation is adjusted to a different range, or when the electronic atomizer is changed and a different electronic atomizer is used, the conversion rate of azelastine hydrochloride is 70% or higher, or 60% or higher. Here, different electronic atomizers are configured to have different heating power or to use different atomizing core components.

[0021] In some embodiments, the liquid formulation further comprises at least one of an edible essence, a sweetener, or a cooling agent.

[0022] The above-mentioned edible essences are intended to enhance the taste and aroma of the aerosol itself, which is formed by atomizing the liquid formulation. The types of edible essences include one or more of the following: fruit flavors, floral flavors, mint flavors, and tea flavors.

[0023] The mass percentage range of the above-mentioned food essence in the liquid formulation is approximately 0-10%, and its specific content can be set to any amount between 0% and 10% depending on the needs of flavor adjustment of the liquid formulation. For example, the mass percentage of the food essence is 5%.

[0024] The above sweetening agent is for enhancing the sweetness of the aerosol generated by atomizing the above liquid preparation. It should be noted that azelastine hydrochloride itself has a certain degree of bitterness. By adding an appropriate amount of sweetening agent to the liquid preparation, it contributes to improving the taste and masking the bitterness of azelastine hydrochloride itself, significantly enhancing the comfort when the user inhales. The type of sweetening agent may be one or more selected from sodium cyclamate, xylitol, mogroside, acesulfame potassium, sodium saccharin, sucralose, aspartame, alitame, neohesperidin dihydrochalcone, neotame, and stevioside.

[0025] The mass percentage range of the above sweetening agent in the liquid preparation is about 0% - 10%, and its specific content can be set to any content within 0% - 10% according to the needs of flavor adjustment of the liquid preparation. For example, the mass percentage content of the sweetening agent in the liquid preparation is 1%.

[0026] The above cooling agent is for enhancing the cooling effect of the aerosol generated by atomizing the above liquid preparation and further enhancing the comfort when the user inhales the aerosol. The cooling agent suitable for use in the above liquid preparation may be one or more of hakatano, menthone, isomenthone, menthols, menthyl ethers, menthyl esters, WS - 23 (2 - isopropyl - N,2,3 - trimethylbutylamide), WS - 3 (N - ethyl - p - menthyl - 3 - carboxamide), WS - 5 (N - (ethoxycarbonylmethyl) - p - alkane - 3 - carboxamide), WS - 12 (N - (4 - methoxyphenyl) - p - menthyl - 3 - carboxamide).

[0027] The mass percentage range of the above cooling agent in the liquid preparation is about 0 - 10%, and its specific content can be set to any content within 0% - 1% according to the needs of flavor adjustment of the liquid preparation. For example, the mass percentage content of the cooling agent in the liquid preparation is 2%.

[0028] One or more edible essences, one or more sweeteners, and one or more cooling agents are added to a liquid preparation containing azelastine hydrochloride and uniformly mixed. The mixing methods include stirring at room temperature, heating and stirring, ultrasonic mixing, stirring by a stirring paddle, magnetic stirring, etc., or other stirring and mixing methods of the prior art are used.

[0029] The embodiments of the present application further provide a cartridge for an electronic atomizer that houses the above liquid preparation.

[0030] The above cartridge may be configured as a separately sellable sealed container that can be assembled into an electronic atomizer. The liquid preparation inside it can flow to the atomization core component in the electronic atomizer and be atomized by the atomization core component to generate an aerosol.

[0031] The above cartridge may be configured as an inseparable member of the electronic atomizer. The liquid preparation inside it can flow to the atomization core component in the electronic atomizer and be atomized by the atomization core component to generate an aerosol. When the liquid preparation inside the cartridge is exhausted, at least a part of the electronic atomizer may be discarded.

[0032] The embodiments of the present application further provide an aerosol generation system including the above liquid preparation and an electronic atomizer for atomizing the liquid preparation to generate an aerosol.

[0033] In some embodiments, the electronic atomizer includes a ceramic core atomizer or a cotton core atomizer.

Brief Description of Drawings

[0034] Hereinafter, in order to more clearly explain the technical solutions of the embodiments of the present invention, the drawings necessary for use in the embodiments of the present invention will be briefly described. Naturally, the drawings described below are only a part of the embodiments of the present invention. A person skilled in the art can conceive of other drawings from these drawings without creative effort. [Figure 1]These are HPLC chromatograms of liquid formulations of azelastine hydrochloride provided in some embodiments of this application. [Figure 2] This is an HPLC chromatogram of an aerosol generated by atomizing a liquid formulation of azelastine hydrochloride provided in some examples of this application. [Figure 3] This is an aerosol particle size distribution diagram of azelastine hydrochloride provided in some embodiments of this application. [Modes for carrying out the invention]

[0035] To facilitate understanding of this application, the application will be described in more detail below with reference to specific embodiments. The embodiments are intended solely to provide a clearer understanding of the technical features, objectives, and effects of this application and do not limit it.

[0036] Unless otherwise noted, the experimental methods used in the following examples are general methods.

[0037] Unless otherwise noted, all materials, equipment, etc., used in the following examples are available through commercial channels.

[0038] In Example 1 of this application, azelastine hydrochloride was prepared as an inhalable liquid formulation, and the stability of the substance itself before and after atomization was analyzed using high-performance liquid chromatography.

[0039] The materials and equipment used in Example 1 are as follows: Ingredients: Azelastine hydrochloride (AH), 1,2-propylene glycol, vegetable glycerin, triethylamine, phosphoric acid, methanol, acetonitrile. Equipment: Shimadzu LC-20A high-performance liquid chromatograph, Labsolutions workstation, Cerulean smoking machine, Sartorius BSA224S electronic balance.

[0040] 1. Prepare a liquid formulation of azelastine hydrochloride. The mass percentages of each component in the liquid formulation were azelastine hydrochloride 0.5%, vegetable glycerin 50%, water 29.5%, and 1,2-propylene glycol 20%.

[0041] 2. Azelastine hydrochloride is atomized and the resulting aerosol is collected. An appropriate amount of liquid formulation was added to an electronic atomizer, drawn in using a Cerulean smoker, and the aerosol was collected using one Cambridge filter. The parameters of the smoker were a suction volume of 55 mL, a suction frequency of 30 s, a suction duration of 3 s, and a suction puff count of 50 puffs. The aerosol collected on the Cambridge filter was collected and extracted by shaking using the initial mobile phase.

[0042] 3. Chromatography conditions Referencing the measurement methods for AH-related substances in the 2015 edition of the Chinese Pharmacopoeia, a Thermo Fisher Acclaim 120 C18 (4.6*250 mm, 5 μm) chromatography column was used. The mobile phase was 4% triethylamine solution (pH adjusted to 6.0 with phosphoric acid)-acetonitrile-methanol (50:18:32), the flow rate was 1.0 mL / min, the detection wavelength was 289 nm, and the column temperature was 30°C.

[0043] Referring to Figure 1, which shows the chromatogram of a liquid formulation of azelastine hydrochloride, and Figure 2, which shows the chromatogram of the aerosol generated by atomizing azelastine hydrochloride, a comparison of Figure 1 and Figure 2 reveals that after atomization, the peak shape of the chromatographic peak of azelastine hydrochloride does not change significantly, and there are almost no extraneous peaks in Figure 2 compared to Figure 1. This indicates that after atomizing azelastine hydrochloride, the substance's components are stable, and the atomization process by electric heating does not decompose the substance's structure, thus not affecting its efficacy.

[0044] In Example 2 of this application, a liquid formulation containing 0.5% azelastine hydrochloride by mass is used as an example, and the conversion rate for generating an aerosol by atomizing azelastine hydrochloride is calculated.

[0045] The materials and equipment used in Example 2 are as follows: Ingredients: Azelastine hydrochloride (AH), 1,2-propylene glycol, vegetable glycerin, triethylamine, phosphoric acid, methanol, acetonitrile. Equipment: Shimadzu LC-20A high-performance liquid chromatograph, Labsolutions workstation, Cerulean smoking machine, Sartorius BSA224S electronic balance.

[0046] 1. Prepare a liquid formulation of azelastine hydrochloride. The mass percentages of each component in the liquid formulation were azelastine hydrochloride 0.5%, vegetable glycerin 50%, water 29.5%, and 1,2-propylene glycol 20%.

[0047] 2. Azelastine hydrochloride is atomized and the resulting aerosol is collected. An appropriate amount of liquid formulation was added to an electronic atomizer, drawn in using a Cerulean smoker, and the aerosol was collected using one Cambridge filter. The parameters of the smoker were a suction volume of 55 mL, a suction frequency of 30 s, a suction duration of 3 s, and a suction puff count of 50 puffs. The aerosol collected on the Cambridge filter was collected and extracted by shaking using the initial mobile phase.

[0048] 3. Chromatographic conditions used in high-performance liquid chromatography Referencing the measurement methods for AH-related substances in the 2015 edition of the Chinese Pharmacopoeia, a Thermo Fisher Acclaim 120 C18 (4.6*250 mm, 5 μm) chromatography column was used. The mobile phase was 4% triethylamine solution (pH adjusted to 6.0 with phosphoric acid)-acetonitrile-methanol (50:18:32), the flow rate was 1.0 mL / min, the detection wavelength was 289 nm, and the column temperature was 30°C.

[0049] 4. Measure the conversion rate of generating an aerosol by atomizing azelastine hydrochloride. 4.1 Prepare a blank control solution and an azelastine hydrochloride liquid formulation, and collect the azelastine hydrochloride aerosol. Blank control: Initial mobile phase. Azelastine hydrochloride liquid preparation: Take an appropriate amount of the liquid preparation and dilute it with the initial mobile phase. Extraction of azelastine hydrochloride aerosol: Take the Cambridge filter used during aerosol collection and extract by shaking using the initial mobile phase.

[0050] 4.2, Calculation method The atomization conversion rate is calculated using the formula A = w1 / w2 * 100%. A=Atomization conversion rate w1 = Mass percentage of azelastine hydrochloride in aerosol w2 = Mass percentage of azelastine hydrochloride in the liquid formulation

[0051] Table 1 below shows the results of atomization conversion rate measurements for a liquid formulation containing 0.5% azelastine hydrochloride by mass.

[0052] JPEG2026511704000001.jpg28156Note: w: Mass percentage of azelastine hydrochloride in aerosol / liquid formulation A: Atomization conversion rate

[0053] Referring to Figure 1, which shows the chromatogram of a liquid formulation containing 0.5% azelastine hydrochloride by mass, and Figure 2, which shows the chromatogram of the aerosol generated by atomizing the above azelastine hydrochloride liquid formulation, the atomization conversion rate of 0.5% azelastine hydrochloride measured by the above calculation method is 97.98. Therefore, the material components of the aerosol formed by converting azelastine hydrochloride are stable, and the conversion efficiency is high.

[0054] In Example 3 of this application, a liquid formulation containing azelastine hydrochloride at a mass percentage of 1% is used as an example, and the conversion rate for generating an aerosol by atomizing azelastine hydrochloride is calculated.

[0055] The materials and equipment used in Example 3 are as follows: Ingredients: Azelastine hydrochloride (AH), 1,2-propylene glycol, vegetable glycerin, triethylamine, phosphoric acid, methanol, acetonitrile. Equipment: Shimadzu LC-20A high-performance liquid chromatograph, Labsolutions workstation, Cerulean smoking machine, Sartorius BSA224S electronic balance.

[0056] 1. Prepare a liquid formulation of azelastine hydrochloride. The weight percentages of each component in the liquid formulation were 1% azelastine hydrochloride, 50% vegetable glycerin, 29% water, and 20% 1,2-propylene glycol.

[0057] 2. Azelastine hydrochloride is atomized and the resulting aerosol is collected. An appropriate amount of liquid formulation was added to an electronic atomizer, drawn in using a Cerulean smoker, and the aerosol was collected using one Cambridge filter. The parameters of the smoker were a suction volume of 55 mL, a suction frequency of 30 s, a suction duration of 3 s, and a suction puff count of 50 puffs. The aerosol collected on the Cambridge filter was collected and extracted by shaking using the initial mobile phase.

[0058] 3. Chromatographic conditions used in high-performance liquid chromatography Referencing the measurement methods for AH-related substances in the 2015 edition of the Chinese Pharmacopoeia, a Thermo Fisher Acclaim 120 C18 (4.6*250 mm, 5 μm) chromatography column was used. The mobile phase was 4% triethylamine solution (pH adjusted to 6.0 with phosphoric acid)-acetonitrile-methanol (50:18:32), the flow rate was 1.0 mL / min, the detection wavelength was 289 nm, and the column temperature was 30°C.

[0059] 4. Measure the conversion rate of generating an aerosol by atomizing azelastine hydrochloride. 4.1 Prepare a blank control solution and an azelastine hydrochloride liquid formulation, and collect the azelastine hydrochloride aerosol. Blank control: Initial mobile phase. Azelastine hydrochloride liquid preparation: Take an appropriate amount of the liquid preparation and dilute it with the initial mobile phase. Extraction of azelastine hydrochloride aerosol: Take the Cambridge filter used for aerosol collection and extract it by shaking using the initial mobile phase.

[0060] 4.2, Calculation method The atomization conversion rate is calculated using the formula A = w1 / w2 * 100%. A=Atomization conversion rate w1 = Mass percentage of azelastine hydrochloride in aerosol w2 = Mass percentage of azelastine hydrochloride in the liquid formulation

[0061] Table 2 below shows the results of atomization conversion rate measurements for liquid formulations containing 1% azelastine hydrochloride by mass.

[0062] JPEG2026511704000002.jpg28156Note: w: Mass percentage of azelastine hydrochloride in aerosol / liquid formulation A: Atomization conversion rate

[0063] The atomization conversion rate of 1% azelastine hydrochloride measured using the above calculation method was 93.54. This indicates that the atomization conversion rate of azelastine hydrochloride in a liquid formulation with a mass percentage content of 1% azelastine hydrochloride is still greater than 90%, and that the components of the aerosol produced by atomizing azelastine hydrochloride by electric heating are stable.

[0064] In Example 4 of this application, a liquid formulation containing 0.5% azelastine hydrochloride by mass is used as an example, and the uniformity of conversion to an aerosol is analyzed by taking multiple inhalations and analyzing the weight of azelastine hydrochloride in the aerosol per puff.

[0065] The mass percentages of each component in the liquid formulation were azelastine hydrochloride 0.5%, vegetable glycerin 50%, 1,2-propylene glycol 20%, and water 29.5%.

[0066] The liquid formulations of the above examples were added to an electronic atomizer, and the mixture was inhaled using a Cerulean smoking machine. The aerosol was collected using one Cambridge filter, and the Cambridge filter was collected once for every 25 puffs inhaled, for a total of 250 puffs inhaled. The measured aerosol conversion rates are shown in Table 3 below.

[0067] JPEG2026511704000003.jpg71156Note: A: Atomization conversion rate

[0068] Table 3 shows that the weight difference of the aerosols collected every 25 puffs was small, and the conversion rate was greater than 90% in all cases. This indicates that the conversion rate of the liquid formulation of azelastine hydrochloride was relatively stable and showed good uniformity.

[0069] It should be explained that the number of puffs set in most currently used electronic atomizers is around 500, and in the above experiment, when the mass stability of azelastine hydrochloride in the aerosol was measured every 25 puffs, it was found to be of good uniformity. Therefore, it has been sufficiently demonstrated that the effect of alleviating unpleasant symptoms is relatively uniform when the user repeatedly inhales the aerosol containing azelastine hydrochloride multiple times, and azelastine hydrochloride is suitable for atomized inhalation using electronic atomizers.

[0070] In Example 5 of this application, the particle size distribution of azelastine hydrochloride aerosol was measured using a smoking machine manufactured by Shenzhen Heyuan Technology Co., Ltd. and a HELOS BR laser particle size analyzer from Sympatec GmbH, Germany.

[0071] The measurement methods used are as follows: An R1 lens (measurement range 0.1 μm to 35 μm) was selected, and logarithmically spaced particle size channels were collected. In the submicron range, there were 10 channels for actual signal measurement, providing very high particle size resolution. For the e-cigarette inhalation mode, the inhalation volume was 55 mL, the inhalation duration was 3 s, and the inhalation interval was 30 s. The inhalation curve was square wave, and each sample was measured three times in parallel, with three puffs each time. The measurement results were averaged, with one time slice every 100 milliseconds, resulting in a total of 30 slices for inhalations of less than 3 seconds, and the flow rate was 18.3 L / min.

[0072] JPEG2026511704000004.jpg23156

[0073] Table 4 shows that the median particle size of the azelastine hydrochloride aerosol was 0.51 μm. Figure 3 shows the particle size distribution of the azelastine hydrochloride aerosol. The aerosols exhibited a unimodal distribution, approximately log-normal, with particle sizes mainly ranging from 0.2 μm to 1.5 μm, and a small number of aerosols ranging from 1.5 μm to 3 μm.

[0074] Because azelastine hydrochloride has a small aerosol particle size, its taste is more delicate.

[0075] Example 5 of this application provides a liquid formulation containing azelastine hydrochloride suitable for atomization using an electronic atomizer, wherein the mass percentage range of azelastine hydrochloride in the liquid formulation is 0.01% to 3%, or the mass percentage range of azelastine hydrochloride in the liquid formulation is 0.1% to 1%.

[0076] When azelastine hydrochloride is used as a tablet, the daily dose for adults is limited to 4 mg or less. Based on the volume of vapor per puff of an e-cigarette and the number of puffs a user takes per day, the azelastine hydrochloride content is controlled to within 3%, allowing users to alleviate unpleasant symptoms of rhinitis and asthma with multiple puffs per day.

[0077] Furthermore, measurements of the atomization effect of liquid formulations of azelastine hydrochloride showed that when the mass percentage of azelastine hydrochloride in the liquid formulation is controlled to approximately 0.1% to 1%, the conversion rate from azelastine hydrochloride in the liquid formulation to an aerosol is almost always over 90%, and sometimes even approaches 100%. Therefore, controlling the mass percentage of azelastine hydrochloride in the liquid formulation to within 0.1% to 1% is advantageous for improving the conversion rate.

[0078] In some examples, the solvent comprises at least one of propylene glycol, vegetable glycerin, water, or ethanol.

[0079] In some examples, the mass percentage of propylene glycol in the inhalation formulation composition is 20% to 80%.

[0080] In some examples, the mass percentage of plant glycerin in the inhalation formulation composition is 30% to 70%.

[0081] The propylene glycol mentioned above can be selected as either 1,2-propylene glycol or 1,3-propylene glycol.

[0082] Propylene glycol and vegetable glycerin are commonly used solvents in electronic atomizers, exhibiting excellent performance in increasing vapor volume and controlling the fluidity of liquid formulations. Therefore, by using propylene glycol and vegetable glycerin as the main solvent components, and simultaneously adding an appropriate amount of water or ethanol as a solvent in proportion to the increase in the mass percentage content of azelastine hydrochloride in the liquid formulation, the solubility of azelastine hydrochloride in the liquid formulation can be increased.

[0083] In some examples, the atomization conversion rate of azelastine hydrochloride is 90% or more, or the atomization conversion rate of azelastine hydrochloride is 80% or more, or the atomization conversion rate of azelastine hydrochloride is 70% or more, or the atomization conversion rate of azelastine hydrochloride is 60% or more.

[0084] Measurements using the atomization measurement method provided in the embodiments of this application show that the atomization conversion rate of a liquid formulation in which azelastine hydrochloride is present within a certain content range is 90% or higher, and this content is generally set to 0.1% to 1% (mass percentage). When the content of azelastine hydrochloride in the liquid formulation is adjusted to a certain range, the conversion rate of azelastine hydrochloride is 80% or higher. Furthermore, when the content of azelastine hydrochloride in the liquid formulation is adjusted to a different range, or when the electronic atomizer is changed and a different electronic atomizer is used, the conversion rate of azelastine hydrochloride is 70% or higher, or 60% or higher. Here, different electronic atomizers are configured to have different heating power or to use different atomizing core components.

[0085] In some embodiments, the liquid formulation further comprises at least one of an edible essence, a sweetener, or a cooling agent.

[0086] The above-mentioned edible essences are intended to enhance the taste and aroma of the aerosol itself, which is formed by atomizing the liquid formulation. The types of edible essences include one or more of the following: fruit flavors, floral flavors, mint flavors, and tea flavors.

[0087] The mass percentage range of the above-mentioned food essence in the liquid formulation is approximately 0-10%, and its specific content can be set to any amount between 0% and 10% depending on the needs of flavor adjustment of the liquid formulation. For example, the mass percentage of the food essence is 5%.

[0088] The above sweetener is intended to enhance the sweetness of the aerosol generated by atomizing the above liquid formulation. It should be explained that azelastine hydrochloride itself has a certain degree of bitterness, so adding an appropriate amount of sweetener to the liquid formulation improves the taste and helps mask the bitterness of azelastine hydrochloride itself, thereby significantly improving the comfort of the user when inhaling. The type of sweetener may be one or more selected from sodium cyclamate, xylitol, mogroside, acesulfame potassium, sodium saccharin, sucralose, aspartame, alitame, neohesperidin dihydrochalcone, neotame, and stevioside.

[0089] The mass percentage range of the sweetener in the liquid formulation is approximately 0% to 10%, and its specific content can be set to any amount between 0% and 10% depending on the needs for flavor adjustment of the liquid formulation. For example, the mass percentage content of the sweetener in the liquid formulation is 1%.

[0090] The above-mentioned cooling agent enhances the cooling effect of the aerosol generated by atomizing the above-mentioned liquid formulation, and further enhances the comfort level when the user inhales the aerosol. Suitable cooling agents for use in the above-mentioned liquid formulation may be one or more of the following: peppermint, menthone, isomenthon, menthol derivatives, menthyl ethers, menthyl esters, WS-23 (2-isopropyl-N,2,3-trimethylbutylamide), WS-3 (N-ethyl-p-menthyl-3-carboxamide), WS-5 (N-(ethoxycarbonylmethyl)-p-alkane-3-carboxamide), and WS-12 (N-(4-methoxyphenyl)-p-menthyl-3-carboxamide).

[0091] The mass percentage range of the above-mentioned cooling agent in the liquid formulation is approximately 0-10%, and its specific content can be set to any amount between 0% and 1% depending on the needs for flavor adjustment of the liquid formulation. For example, the mass percentage content of the cooling agent in the liquid formulation is 2%.

[0092] A liquid formulation containing azelastine hydrochloride is mixed uniformly with one or more food essences, one or more sweeteners, and one or more cooling agents. The mixing method includes stirring at room temperature, heating and stirring, ultrasonic mixing, stirring with a stirring paddle, magnetic stirring, or other conventional stirring and mixing methods.

[0093] It should be explained that the inventors measured the atomization performance of more than 20 types of pharmaceuticals and found that most pharmaceuticals are unsuitable for atomization inhalation using an electronic atomizer. For example, the atomization conversion rate of clenbuterol hydrochloride is less than 10%, the atomization conversion rate of sodium cromoglycate is less than 15%, and the atomization conversion rate of terbutaline sulfate is less than 50%. Due to the low conversion rate, the content of the active ingredient in the aerosol is low, and even if the user inhales it multiple times, it is difficult to obtain an effect that alleviates unpleasant symptoms. On the other hand, the liquid formulation containing azelastine hydrochloride provided in the examples of this application has a high conversion rate and high uniformity in converting the active ingredient into an aerosol after atomization using an electronic atomizer, resulting in unexpected technical effects. Therefore, it is suitable for preparation as a liquid formulation and atomization using an electronic atomizer to generate an aerosol, allowing the user to inhale the aerosol and alleviate unpleasant symptoms.

[0094] Example 6 of this application provides a cartridge for an electronic atomizer that contains a liquid formulation containing azelastine hydrochloride.

[0095] The above cartridge may be configured as a sealed container that can be sold separately and assembled into an electronic atomizer, and the liquid formulation inside can flow into the atomizing core component in the electronic atomizer, where it can be atomized by the atomizing core component to generate an aerosol.

[0096] The above-mentioned cartridge may be configured as an inseparable component of the electronic atomizer, and the liquid formulation inside it flows to the atomizing core component in the electronic atomizer, where it is atomized to generate an aerosol. When the liquid formulation inside the cartridge is completely consumed, at least a part of the electronic atomizer may be discarded.

[0097] Embodiment 7 of this application provides an aerosol generation system comprising the above-mentioned liquid formulation and an electronic atomizer for atomizing the liquid formulation to generate an aerosol.

[0098] In some embodiments, the electronic atomizer includes a ceramic core atomizer or a cotton core atomizer.

[0099] A ceramic core atomizer includes a porous fluid guide and a heating element coupled to the porous fluid guide. The porous fluid guide is made from a porous material, which includes microporous ceramics, microporous glass ceramics, microporous glass, or foamed metals. The heating element may be a metallic material, metal alloy, graphite, carbon, conductive ceramic, or a composite material of a metallic material and other ceramic materials having appropriate impedance. Suitable metallic or alloy materials include at least one of nickel, cobalt, zirconium, titanium, nickel alloys, cobalt alloys, zirconium alloys, titanium alloys, nickel-chromium alloys, nickel-iron alloys, iron-chromium alloys, titanium alloys, iron-manganese-aluminum alloys, or stainless steel.

[0100] The cotton core atomizer includes a fluid guide element and a heating element coupled to the fluid guide element. The fluid guide element is made of fibrous cotton, and the manufacturing material of the heating element in the cotton core atomizer is almost the same as the manufacturing material of the heating element in the ceramic core atomizer.

[0101] An electronic atomizer includes not only an atomizing core component but also a battery component for supplying power for operation.

[0102] The electronic atomizer is preferably configured as a small, portable device that is easy for the user to carry with them at any time and can be used to alleviate unpleasant symptoms of rhinitis and asthma at any time.

[0103] Finally, it should be noted that the above embodiments are merely illustrative and not restrictive. Under the concept of the present invention, the technical features of the above embodiments or different embodiments can be combined, the steps can be implemented in any order, and many other variations of the different aspects of the present invention described above exist, which will not be described in detail for the sake of brevity. While the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that modifications to the technical solutions described in each of the above embodiments, or equivalent substitutions of some of their technical features, are still possible. These modifications or substitutions will not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of each embodiment of the present invention.

Claims

1. Solvent and, A liquid formulation that can be used for atomization by an electronic atomizer, characterized by containing azelastine hydrochloride.

2. A liquid formulation usable for atomization by an electronic atomizer, characterized in that the mass percentage of azelastine hydrochloride in the liquid formulation is 0.01% to 3%, or the mass percentage of azelastine hydrochloride in the liquid formulation is 0.1% to 1%.

3. The solvent comprises at least one of propylene glycol, vegetable glycerin, water, or ethanol, making it a liquid formulation usable for atomization by an electronic atomizer as described in claim 1.

4. A liquid formulation usable for atomization by an electronic atomizer, characterized in that the mass percentage of propylene glycol in the liquid formulation is 20% to 80%.

5. A liquid formulation usable for atomization by an electronic atomizer, characterized in that the mass percentage of the plant glycerin in the liquid formulation is 30% to 70%.

6. The atomization conversion rate of the aforementioned azelastine hydrochloride is 90% or more. Alternatively, the atomization conversion rate of the aforementioned azelastine hydrochloride is 80% or more. Alternatively, the atomization conversion rate of the aforementioned azelastine hydrochloride is 70% or more. Alternatively, a liquid formulation usable for atomization by an electronic atomizer according to claim 1, characterized in that the atomization conversion rate of the azelastine hydrochloride is 60% or more.

7. The liquid formulation usable for atomization by an electronic atomizer according to claim 1, characterized in that the particle size range of the aerosol generated when azelastine hydrochloride in the liquid formulation usable for atomization by the electronic atomizer is atomized by the electronic atomizer is 0.2 μm to 3 μm.

8. The liquid formulation is characterized in that it further comprises at least one of an edible essence, a sweetener, or a cooling agent, and is a liquid formulation usable for atomization by an electronic atomizer according to claim 1.

9. A cartridge for an electronic atomizer, characterized in that it contains a liquid formulation that can be used for atomization by an electronic atomizer according to any one of claims 1 to 8.

10. An aerosol generating system comprising a liquid formulation usable for atomization by an electronic atomizer according to any one of claims 1 to 8, and an electronic atomizer for atomizing the liquid formulation to generate an aerosol.

11. The aerosol generating system according to claim 10, characterized in that the electronic atomizer includes a ceramic core atomizer or a cotton core atomizer.

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