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WO2023071872A1 - 液体制剂及其制备方法、气溶胶生成系统、用于气溶胶生成系统的筒以及气溶胶生成装置 - Google Patents

液体制剂及其制备方法、气溶胶生成系统、用于气溶胶生成系统的筒以及气溶胶生成装置 Download PDF

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Publication number
WO2023071872A1
WO2023071872A1 PCT/CN2022/126035 CN2022126035W WO2023071872A1 WO 2023071872 A1 WO2023071872 A1 WO 2023071872A1 CN 2022126035 W CN2022126035 W CN 2022126035W WO 2023071872 A1 WO2023071872 A1 WO 2023071872A1
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WIPO (PCT)
Prior art keywords
yohimbine
liquid preparation
liquid
extract
aerosol
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PCT/CN2022/126035
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English (en)
French (fr)
Inventor
邓晶晶
徐中立
李永海
Original Assignee
深圳市合元科技有限公司
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Application filed by 深圳市合元科技有限公司 filed Critical 深圳市合元科技有限公司
Priority to JP2024523461A priority Critical patent/JP2024539101A/ja
Priority to EP22885750.4A priority patent/EP4393481A1/en
Priority to KR1020247017695A priority patent/KR20240091076A/ko
Publication of WO2023071872A1 publication Critical patent/WO2023071872A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/02—Sprayers or atomisers specially adapted for therapeutic purposes operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A61M11/041—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters
    • A61M11/042—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters electrical

Definitions

  • the present application relates to the field of atomization technology, and in particular to a liquid formulation containing yohimbine, a preparation method of the liquid formulation, an aerosol generating system, a cartridge for the aerosol generating system, and an aerosol generating device.
  • An aerosol-generating system includes an aerosol-generating device, and a liquid formulation stored within the aerosol-generating device. Aerosol-generating devices form an aerosol by atomizing a liquid formulation. Liquid formulations mainly include glycerin and 1,2-propanediol, as well as synthetic flavors, nicotine and/or nicotine salts, etc. In addition to being used as a substitute for traditional burning cigarette products, the aerosol generating system can also be used as an adjuvant therapy.
  • the main method is to add health-care ingredients to liquid preparations, and the health-care ingredients are formed by atomization. Aerosols are inhaled by users. In recent years, the big health industry has developed rapidly, and liquid preparations with health-care ingredients have attracted more and more attention from researchers and consumers. Select health-care ingredients that are really beneficial to users and add them to liquid preparations, and make the health-care ingredients It is the focus of attention to play its role.
  • Yohimbe is a herbal plant with a history of hundreds of years in Africa. There are also many health products on the market that use yohimbe extract as raw materials.
  • yohimbine extract often exists in the form of yohimbine hydrochloride, but the solubility of yohimbine hydrochloride in liquid preparations of glycerol-propylene glycol system is low, and it is very easy to separate out and form a turbid liquid, which leads to It is difficult for yohimbine to be converted into aerosol and inhaled by users, which greatly hinders the use of yohimbine extract in aerosol generating systems.
  • an embodiment of the present application provides a liquid preparation for an aerosol generating system, the liquid preparation includes yohimbe extract, solubilizer, and solvent; wherein, the dissolving power of the yohimbine extract in the solubilizer is greater than the solvent power of the yohimbine extract in the solvent; the yohimbine extract After being dissolved in the solubilizer, it can form a stable and transparent solution with the solvent.
  • the mass percentage content of the yohimbine extract is 0.01-15%; the mass percentage content of the solubilizer is 0.09-15%; the solvent The mass percent content is 50-99.9%.
  • the yohimbine extract includes yohimbine.
  • the yohimbine and the solubilizing agent form a yohimbine concentrate; based on the weight percentage of the liquid preparation, the mass percentage of the yohimbine concentrate is 0.1-30%.
  • the solvent includes glycerin and propylene glycol.
  • the mass percent content of the yohimbine extract is 0.015-12%; or, the mass percent content of the yohimbine extract is 0.02-12% %.
  • the solubilizer includes at least one of benzyl alcohol and an organic acid.
  • the solubilizer further includes water.
  • the organic acid includes at least one of lactic acid, glacial acetic acid, adipic acid, fumaric acid, tartaric acid, malic acid, citric acid and benzoic acid.
  • the mass percentage content of the benzyl alcohol is 0-27%; or, the mass percentage content of the benzyl alcohol is 0.008-15%; or, the The mass percent content of benzyl alcohol is 0.012-9%.
  • the mass percentage content of the organic acid is 0-24%; or, the mass percentage content of the organic acid is 0.008-15%; or, the The mass percent content of the organic acid is 0.012-9%.
  • the mass percentage content of the water is 0-24%; or, the mass percentage content of the water is 0.01-15%; or, the water content The mass percentage content is 0.02-12%.
  • the liquid formulation further includes at least one of a sweetener, a cooling agent, and a flavor composition.
  • the embodiment of the present application also provides a method for preparing the above-mentioned liquid preparation, including the following steps: preparing yohimbine; adding yohimbine to the solubilizer, so that yohimbine is fully dissolved in the solubilizer to obtain yohimbine Concentrate; add yohimbine concentrate to solvent.
  • the yohimbine base is prepared by acidifying yohimbine hydrochloride.
  • the present application also provides a cartridge for an aerosol generating system, the cartridge containing the above-mentioned liquid formulation.
  • the present application also provides an aerosol generating system, comprising the above-mentioned cartridge and an aerosol generating device, the aerosol generating device is configured to receive at least a part of the cartridge, and is used to atomize the liquid preparation to form an aerosol generating device.
  • an aerosol generating system comprising the above-mentioned cartridge and an aerosol generating device, the aerosol generating device is configured to receive at least a part of the cartridge, and is used to atomize the liquid preparation to form an aerosol generating device.
  • the embodiment of the present application also provides an aerosol generating device, which includes an atomizer and a chamber containing the above-mentioned liquid preparation, and the atomizer is used to atomize the liquid preparation to generate an aerosol.
  • the beneficial effect of the embodiment of the present application is: in the above liquid preparation, by dissolving the yohimbine extract in the solubilizing agent, since the dissolving ability of the yohimbine extract in the solubilizing agent is greater than its dissolving ability in the solvent, the yohimbine extract After the yohimbine extract is dissolved in the solubilizer, it can form a stable and transparent solution with the solvent in the liquid preparation, thereby increasing the amount of yohimbine extract used in the aerosol generating system and promoting the use of yohimbine extract in the aerosol generating system Applications.
  • Fig. 1 is the HPLC spectrogram of yohimbine hydrochloride (a) and yohimbine soda ash (b) before and after the deacidification process treatment that the embodiment of the application provides;
  • Fig. 2 is the HPLC spectrogram of the aerosol formed by the atomization of yohimbine hydrochloride and yohimbine soda ash provided by the examples of the present application;
  • Fig. 3 is a comparison chart of the dissolution of three solutions of liquid preparation a, liquid preparation b and liquid preparation c provided in the examples of the present application;
  • Figure 4 is a comparison chart of the conversion rates of four groups of yohimbine provided in Example 11 of the present application.
  • Yohimbine extract is an active substance extracted from the bark of a natural plant "YOHIMBE" yohimbe grown in Africa. Yohimbine can act on the sexual organs, can expand the blood vessels of the sexual organs, increase the blood flow of the sexual organs, increase the formation of nitrous oxide, and thus enhance sexual function. This is a relatively certain and most widely used plant-based pure plant preparation for treating erectile dysfunction, and can prevent prostate hypertrophy and urinary system infection.
  • the yohimbine extract is added to the liquid preparation used in the aerosol generating system, and the aerosol is formed by atomization through the aerosol generating device, and the user can make the yohimbine exert its functional curative effect by inhaling the aerosol. Therefore, applying yohimbine to the field of aerosol generating system can greatly expand the health use effect of the aerosol generating device.
  • Yohimbine extracts include yohimbine hydrochloride and yohimbine.
  • the chemical formula of yohimbine is C21H26N2O3, easily soluble in chloroform, soluble in methanol and ethanol, slightly soluble in water.
  • the commercially available yohimbine extract mainly exists in the form of yohimbine hydrochloride.
  • the chemical formula of yohimbine hydrochloride is C21H27CLN2O3. It is easily soluble in chloroform, soluble in methanol and ethanol, and slightly soluble in water.
  • yohimbine hydrochloride and yohimbine base have extremely low solubility in the solvents of glycerin and propylene glycol systems, and the addition amount of yohimbine hydrochloride and yohimbine base is far lower than 1 %, there will be crystal precipitation. Since yohimbine extract is difficult to dissolve in solvents, it is difficult for yohimbine to be converted into aerosol and inhaled by users.
  • Example 1 of the present application provides a liquid preparation containing yohimbine extract for use in an aerosol generating system.
  • the liquid formulation includes solvent, yohimbine concentrate.
  • Yohimbine extract is found in yohimbine concentrate.
  • the yohimbine concentrate can form a stable and transparent solution with the solvent of the glycerol-propylene glycol system, thereby solving the problem that the yohimbine extract is difficult to dissolve in the glycerin-propylene glycol system solvent.
  • the mass percentage content of the yohimbine concentrated solution is 0.1-30%; the mass percentage content of the solvent is 50-99.9%.
  • the yohimbine concentrate comprises yohimbine extract, and the mass percentage content of the yohimbine extract is 0.01-15% by weight of the liquid preparation; or the mass percentage content of the yohimbine extract is 0.015-12% ; Or the mass percent content of yohimbine extract is 0.02-12%.
  • the mass percent of the yohimbine extract is 10-50% based on the weight percentage of the yohimbine concentrate; optionally, the mass percent of the yohimbine extract is 15% -40%; Furthermore, the mass percentage of yohimbe extract can also be 20-40%.
  • the mass percent of yohimbine extract is 0.01-15%; optionally, the mass percent of yohimbine extract is 0.015-12%; further, the yohimbine extract The mass percentage of the substance can be 0.02-12%.
  • the specific amount of yohimbe extract added can be adjusted according to the needs of users, for example, based on the weight percentage of the liquid preparation, the mass percentage of yohimbine extract can be 1%, 2%, 5% , 6%, 8%, 10%, 12%, 14% or any value between 0.01-15%. Since yohimbine extract can be dissolved in a large amount of solubilizer to form yohimbine concentrate, by adjusting the ratio of yohimbine concentrate in the liquid preparation, you can arbitrarily change the yohimbine extract in the liquid preparation the added amount.
  • Implementation 1 of the present application also provides a part of the specific component formulations for preparing the above-mentioned liquid preparation.
  • the mass percent content of each component is shown in Table 1 below in terms of the total amount of the liquid preparation.
  • the yohimbine extract is mainly present in the yohimbine concentrate in the form of yohimbine base.
  • the solvent mainly includes glycerin and propylene glycol, and the two components of glycerin and propylene glycol can be mixed in any proportion.
  • the solvent may also include butanediol, 1,2,4-butanetriol, dipropylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol 200, polyethylene glycol 400 , glyceryl triacetate, dipropylene glycol ether, ethanol, water, triethyl citrate, glyceryl caprylate or one or more of them.
  • the specific solvent selection needs to be optimized according to the type of components added to the solvent. Glycerin and propylene glycol are preferred components in the solvent from the standpoint of improving the quality of the aerosol produced by the aerosol generating device.
  • yohimbine hydrochloride is deacidified to form yohimbine.
  • the deacidification process of organic matter can be carried out by oxidation or acid-base neutralization, wherein the acid-base neutralization method includes esterification. Now take the esterification reaction as an example for specific description.
  • the deacidification treatment process of yohimbine hydrochloride mainly includes the following steps:
  • yohimbine hydrochloride powder into ethyl acetate; after it is fully dissolved, transfer it into a separatory funnel, add purified water, fully shake the separatory funnel, mix evenly, and let it stand for stratification.
  • the ratio of yohimbine hydrochloride to ethyl acetate is 1:(40-70); calculated by volume ratio, the ratio of pure water to ethyl acetate is 1:(2-3).
  • the second step is to adjust the pH and filter
  • a water layer and an ethyl acetate layer are formed, wherein the upper layer is an ethyl acetate layer, and the lower layer is a water layer; add enough sodium hydroxide solution, and fully shake the separatory funnel until the pH value of the mixture is about 9 ; After standing for stratification, release the water in the lower layer.
  • Example 3 whether the deacidification treatment process in Example 2 affects the functional components of yohimbine was analyzed through detection and comparison.
  • the detection and analysis method is as follows: add yohimbine hydrochloride before the deacidification process and yohimbine after the deacidification process into the liquid chromatograph, and compare and analyze the deacidification process to verify the effect of the deacidification process on the yohimbine hydrochloride. Whether the functional components of yohimbine have an effect.
  • the comparative analysis methods of liquid chromatography are described in detail as follows:
  • Chromatographic conditions DGU-20A5R liquid chromatograph, reversed-phase column C18, 4.6x250mm, 3.5um; mobile phase: acetonitrile-water (volume ratio: 30:70); column temperature 35°C, flow rate 1.0 mL/min; detection wavelength 278nm, injection 10 ⁇ L.
  • Example 4 the yohimbine hydrochloride before the deacidification process was further formulated into an atomized liquid formulation 1 and the yohimbine after the deacidification process was formulated into an atomized liquid formulation 2; Add liquid preparation 1 to the aerosol generating device and atomize to obtain aerosol 1, add liquid preparation 2 to the aerosol generating device to obtain aerosol 2; and use liquid chromatography to compare and analyze the performance of aerosol 1 and aerosol 2 .
  • the comparative analysis method of the specific liquid chromatography is the same as that of the above-mentioned solution 1 and solution 2, with reference to the following description:
  • Chromatographic conditions DGU-20A5R liquid chromatograph, reversed-phase column C18, 4.6x250mm, 3.5um; mobile phase: acetonitrile-water (volume ratio: 30:70); column temperature 35°C, flow rate 1.0 mL/min; detection wavelength 278nm, injection 10 ⁇ L.
  • the yohimbine base obtained through the above deacidification treatment process is formulated into a yohimbine concentrate.
  • the formulation of yohimbine concentrate is provided in Example 5 of the present application.
  • the yohimbine concentrate includes yohimbine and a solubilizer, wherein the yohimbine can be fully dissolved in the solubilizer to form a stable and transparent solution without yohimbine precipitates.
  • Solubilizers include benzyl alcohol, organic acids and water. Among them, benzyl alcohol and organic acid are preferred components as solubilizers.
  • the organic acid includes but not limited to one or more mixtures of lactic acid, glacial acetic acid, adipic acid, fumaric acid, malic acid, citric acid and benzoic acid. Lactic acid and glacial acetic acid are preferred among the organic acids.
  • yohimbine can form intermolecular hydrogen bonds with benzyl alcohol or organic acids, thereby promoting the dissolution of yohimbine in benzyl alcohol or organic acid solvents. dissolve.
  • yohimbine is a polar organic substance
  • benzyl alcohol, glacial acetic acid and lactic acid are polar organic solvents, which can promote the dissolution of benzohimbine in the above two types of substances.
  • the polarity of propylene glycol and glycerol is less than that of benzyl alcohol, glacial acetic acid, and water.
  • polar yohimbine is more easily soluble in the mixture of benzyl alcohol, glacial acetic acid, lactic acid, and water with stronger polarity. in the solubilizer formed.
  • the mass percent of yohimbine is 10-50%; optionally, the mass percent of yohimbine is 15-40%; further, the mass percent of yohimbine The mass percentage can also be 20-40%.
  • the mass percent of benzyl alcohol is 0-90% based on the weight percentage of the yohimbine concentrated solution; optionally, the mass percent of benzyl alcohol is 8-50%; further, the benzene The mass percentage of methanol can also be 12-30%.
  • the mass percentage of the organic acid is 0-80% based on the weight percentage of the yohimbine concentrate; optionally, the mass percentage of the organic acid is 8-50%; further, the organic acid The mass percentage of acid can also be 12-30%.
  • the mass percent of water in terms of weight percentage of the yohimbe concentrated solution, the mass percent of water is 0-80%; optionally, the mass percent of water is 10-50%; further, the mass percent of water The percentage can also be 20-40%.
  • the solubilizer can be selected from any organic substance that can promote the dissolution of yohimbine or yohimbine hydrochloride, but the solubilizer needs to meet the nebulization function requirements of the nebulized liquid preparation of the aerosol generating system. At the same time as the inhaled aerosol, it does not affect the performance of the aerosol formed by the atomization of the liquid preparation, which includes mouthfeel, smoke stability and the health of the user.
  • the mass percentage of benzyl alcohol is 0-27%; optionally, the mass percentage of benzyl alcohol is 0.008-15%; optionally, the mass percentage of benzyl alcohol is 0.012-9%. It can be understood that the specific added dosage of benzyl alcohol can be adaptively adjusted according to the requirement of the added amount of yohimbine to be dissolved, and the mass ratio content of benzyl alcohol can be any value between 0-27%.
  • the mass percentage of the organic acid is 0-24%; optionally, the mass percentage of the organic acid is 0.008-15%; optionally, the mass percentage of the organic acid
  • the content is 0.012-9%. It can be understood that the specific added dosage of the organic acid can be adaptively adjusted according to the requirement of the added amount of yohimbine to be dissolved, and the mass ratio content of the organic acid can be any value between 0-24%.
  • adaptive adjustment can be made according to the content requirements of the yohimbine extract to be added, and is not limited to the above-mentioned content range. For example, if the content requirement of the yohimbe extract in the liquid preparation used for the aerosol production system is 3% (by mass percentage), in the liquid preparation, the content of the yohimbine concentrate is 15% (by mass %) percentage), then in the yohimbe concentrate, the content of yohimbine extract is 20% (by mass percentage), and the content of solubilizer is 80% (by mass percentage).
  • Example 6 of the present application the preparation process of the above-mentioned yohimbine concentrate is also provided, including the following steps:
  • Yohimbine can be completely dissolved in the yohimbine concentrate prepared by some formulations, and yohimbine cannot be completely dissolved in the yohimbine concentrate prepared by some formulations, and there will be some trace amounts of yohimbine in the concentrate at this time Suspended matter or some undissolved crystal nuclei, in order to obtain a stable yohimbine concentrate, it is necessary to select the number of operations in step 5 according to the situation of the prepared concentrate, so as to fully filter the impurities in the prepared yohimbine concentrate.
  • Example 5 of the present application also provides a part of the specific component formula for preparing the above-mentioned yohimbine concentrate, refer to Table 2 below.
  • Table 1 only lists a part of the formula for preparing the yohimbine concentrate.
  • the specific yohimbine extract can be Adaptive adjustments are made to the concentration requirements.
  • Example 7 of the present application further comparatively analyzed the solubility of the atomized solution in which different yohimbine extracts were added to the glycerol-propylene glycol system solvent.
  • the specific analysis method is as follows:
  • Liquid preparation a Liquid preparation b liquid preparation c dissolved state insoluble insoluble solution transparent
  • liquid preparation a and liquid preparation b solution are turbid, show that yohimbine hydrochloride has very little solubility in the glycerol-propylene glycol system solvent, and the yohimbine that has entered the deacidification process preparation is in glycerol-propylene glycol system solvent.
  • the solubility in the propylene glycol system solvent is also very small; while the liquid preparation c solution is clear and transparent, and the liquid preparation c is observed after standing for a period of time, the solution c is still transparent, and no crystals are precipitated, indicating that the yohimbine provided in Example 5 of the present application
  • the concentrate can form a stable and transparent solution system in the glycerin-propylene glycol system solvent.
  • the problem of adding yohimbine in liquid preparations can be solved by formulating yohimbine into yohimbine concentrate, and the addition amount of yohimbine extract can be increased according to the specific use requirements. At the same time, the prepared atomized liquid preparation has good stability and no Precipitate out.
  • Example 9 of the present application further comparatively analyzed the effect of conversion rate of liquid preparations containing different yohimbine extracts into aerosol yohimbine in an aerosol generating device.
  • liquid preparation 3 is atomized in the aerosol generating device to form aerosol 3
  • liquid preparation 4 is atomized in the aerosol generating device Aerosol formation 4.
  • the liquid preparation 3 is prepared by adding yohimbine hydrochloride to the glycerol-propylene glycol system solvent. Calculated by weight percentage of the liquid preparation 3, the mass percentage of yohimbine hydrochloride is 1%, the mass percentage of propylene glycol is 49%, and the mass percentage of glycerin 50%.
  • Liquid preparation 4 is prepared by adding yohimbine concentrate to the glycerol-propylene glycol system solvent. Calculated by weight percentage of liquid preparation 4, the mass percentage of yohimbe concentrate is 30%, the mass percentage of propylene glycol is 20%, glycerin The mass percentage is 50%. Wherein, in the yohimbine concentrate used in the liquid preparation 4, the mass percentage content of yohimbine is 3.33% based on the weight of the yohimbine concentrate, which can be obtained by calculation, and calculated by the weight of the liquid preparation 4, The mass percent content of yohimbine is 1%.
  • Embodiment 10 of the present application provides an aerosol generating device for an aerosol generating system
  • the aerosol generating device includes an atomizer with an atomizing function.
  • the nebulizer includes a heating element and a liquid guiding element.
  • the liquid guide element can absorb and deliver the liquid formulation, and the heating element can atomize the liquid formulation to form an aerosol.
  • the atomizer includes a ceramic core atomizer and a cotton core atomizer.
  • the liquid guide element can be made of materials with capillary structure and excellent liquid storage performance, such as non-woven fabrics, cotton, etc.
  • the heating element can be a spiral heating wire or a heating net made of at least one of stainless steel, nickel-chromium alloy, iron-chromium-aluminum alloy, metal titanium, etc.; the liquid guiding element can be fixedly arranged on the spiral heating wire or heating net outside; alternatively, a helical heating wire or heating mesh is disposed around at least part of the surface of the liquid guiding element.
  • the liquid-guiding element can be a porous body structure made of a hard capillary structure such as porous ceramics, porous glass ceramics, or porous glass. The liquid-guiding element is roughly block-shaped, and at least part of the surface of the liquid-guiding element The heating element is fixed on it.
  • the heating element can be one of heating coating, heating sheet or heating net.
  • the heating coating may include, but not limited to, electromagnetic induction heating coating, infrared induction heating coating, and the like.
  • the heating element can be sintered on the surface of the porous body after printing and using conductive raw material powder mixed with printing aids to form a slurry.
  • Example 9 of the present application the influence of the ceramic atomizer and the cotton core atomizer on the conversion rate of yohimbine in the liquid preparation was further analyzed comparatively.
  • Embodiment 9 of the present application tests and analyzes the conversion rate of yohimbine in aerosol 3 and aerosol 4, and the test method used refers to the following description:
  • the test method includes the following steps: using a smoking machine to perform a suction test on the liquid preparation 3 and the liquid preparation 4 respectively according to international standards.
  • the specific suction test conditions are: each suction time is 3 seconds, the suction time interval is 30 seconds, the number of suctions is 50 times, and the amount of the liquid preparation for each suction is 55 mL. Aerosol 3 and Aerosol 4 were collected separately with Cambridge filters.
  • W% is the conversion efficiency of yohimbine
  • C 0 is the concentration of the aerosol captured by the Cambridge filter
  • C 1 is the concentration of the liquid preparation
  • a 0 is the chromatogram of yohimbine in the aerosol Peak area
  • a 1 is the chromatographic peak area of yohimbine in the liquid preparation
  • m 0 is the mass of the aerosol (i.e. the mass difference before and after the Cambridge filter is captured)
  • m 1 is the quality of the liquid preparation
  • V is the volume of the extraction solvent .
  • Example 9 the liquid preparation 3 was respectively added to the aerosol generating device 1 equipped with a cotton core atomizer of the same specification, and the aerosol generating device 2 equipped with a ceramic atomizer of the same specification;
  • the liquid preparation 4 is respectively added to the aerosol generating device 3 equipped with a cotton nebulizer of the same specification, and the aerosol generating device 4 equipped with a ceramic atomizer of the same specification. Then the above-mentioned aerosol generating device 1, aerosol generating device 2, aerosol generating device 3, and aerosol generating device 4 are respectively connected to the same smoking machine, and the first group of aerosols and the second group of aerosols are respectively obtained according to the above-mentioned suction test method.
  • Aerosols Group III Aerosols, and Group IV Aerosols.
  • use the same organic solvent to extract the yohimbine hydrochloride sample 1 in the first group of aerosols use the same organic solvent to extract the yohimbine hydrochloride sample 2 in the second group of aerosols, and use the same organic solvent to extract the third group Yohimbine sample 3 in the aerosol, using the same organic solvent to extract the fourth group of yohimbine sample 4 in the aerosol.
  • the chromatographic peak area is A 02
  • the chromatographic peak area of yohimbine obtained from sample 3 is A 03
  • the chromatographic peak area of yohimbine obtained from sample 4 is A 04 .
  • Liquid formulation 3 and liquid formulation 4 are prepared, wherein the mass of liquid formulation 3 is m 13 , and the mass of liquid formulation 4 is m 14 .
  • the above-mentioned liquid preparation 3 and liquid preparation 4 were respectively added to a liquid chromatograph for liquid chromatography analysis operation, and the chromatographic peak area corresponding to yohimbine in liquid preparation 3 was obtained as A 13 , and the yohimbine in liquid preparation 4 was obtained The chromatographic peak area corresponding to the guest is A 14 .
  • a 01 and A 13 are brought into the calculation formula of the above-mentioned conversion rate, and the hydrochloric acid in the first group of aerosols formed by the atomization of the yohimbine hydrochloride liquid preparation in the aerosol generating device 1 equipped with a cotton core atomizer is obtained.
  • the conversion efficiency of yohimbine; A 02 and A 13 are brought into the calculation formula of the above-mentioned conversion rate, and the yohimbine hydrochloride liquid preparation is atomized and formed in the aerosol generating device 2 equipped with a ceramic core atomizer.
  • the conversion rate of yohimbine is 36%, and the conversion rate of yohimbine is 36%.
  • the conversion rate of yohimbine is 56%, even if the liquid preparation prepared by the yohimbine concentration process provided in the embodiment of the present application can significantly increase the yohimbine in the aerosol content.
  • the content of yohimbine in the aerosol formed by atomization using an aerosol generating device equipped with a ceramic atomizer is N1
  • the content of yohimbine in the aerosol formed by using an aerosol generating device equipped with a cotton core atomizer is N1.
  • the content of yohimbine in the aerosol formed by the atomization of the sol generating device is N2, N1>N2. Therefore, the aerosol generating device equipped with a ceramic core atomizer has a better atomization effect on the liquid preparation containing yohimbine, and can increase the conversion rate of yohimbine.
  • Example 11 of the present application also provides a liquid formulation containing yohimbine for use in an aerosol generating system.
  • Liquid formulations include yohimbine concentrates, solvents, sweeteners, cooling agents and flavor compositions. Based on the weight of the liquid preparation, the mass percentage content of the yohimbine concentrated solution is 0.1-30%; the mass percentage content of the solvent is 50-99.9%; the mass percentage content of the sweetener is 0.01-0.5%; the cooling agent The mass percentage content is 0.01-8%; the mass percentage content of the flavor composition is 0.01-15%.
  • the solvent includes but is not limited to propylene glycol, glycerin, butanediol, 1,2,4-butanetriol, dipropylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, One or more of Glycol 200, Polyethylene Glycol 400, Glyceryl Triacetate, Dipropylene Glycol Ether, Ethanol, Water, Triethyl Citrate and Glyceryl Caprylate.
  • the cooling agent includes but is not limited to menthol, menthone, isomenthone, WS-23 (2-isopropyl-N,2,3-trimethylbutanamide ), WS-3 (N-ethyl-p-menthyl-3-carboxamide), WS-5 (N-(ethoxycarbonylmethyl)-p-alkane-3-carboxamide), menthyl lactate and menthone
  • menthol menthone
  • isomenthone 2,3-trimethylbutanamide
  • WS-3 N-ethyl-p-menthyl-3-carboxamide
  • WS-5 N-(ethoxycarbonylmethyl)-p-alkane-3-carboxamide
  • menthyl lactate menthone
  • the sweetener includes but is not limited to one or a combination of neotame, cyclamate, sucralose, aspartame, steviol glycoside and acesulfame K, The total addition amount is 0.01-0.5% (based on mass percentage content).
  • the flavor composition is a natural or synthetic flavor and fragrance, including but not limited to fruit, floral, tea, mint, coffee, soda, candy or tobacco flavors. Adding a flavor composition can be used to enrich the mouthfeel of the aerosol formed by atomization of the liquid preparation.
  • Embodiment 12 of the present application also provides an aerosol generating device, the aerosol generating device is equipped with a cartridge capable of containing the liquid preparation provided in any embodiment of the present application, and the liquid preparation contains yohimbine extract.
  • the aerosol generating device is equipped with an atomizer that can atomize the liquid preparation to form an aerosol and a control module that can make the aerosol release stably.
  • the aerosol output channel of the aerosol is output to the outside of the aerosol generating device for the user to inhale.
  • the aerosol generating device can also atomize the liquid preparation in other forms to form an aerosol to be effectively delivered to the user.
  • the atomization temperature is optimized and selected, and the specific atomization form is not limited.
  • the aerosol generating device can be atomized by a resistance and/or electromagnetic heating element; in other embodiments, it can be ultrasonic atomization, or electric heating atomization and ultrasonic atomization can be carried out simultaneously; in some In an embodiment, the aerosol generating device can also be an air compressed atomizing device or a push-type spraying device.

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Abstract

本申请公布了一种液体制剂、液体制剂的制备方法、气溶胶生成系统、用于气溶胶生成系统的筒以及气溶胶生成装置，所述液体制剂包括育亨宾提取物、促溶剂和溶剂；其中，所述育亨宾提取物在所述促溶剂中的溶解能力大于所述育亨宾提取物在所述溶剂中的溶解能力；所述育亨宾提取物溶解于所述促溶剂后能够与所述溶剂形成稳定透明的溶液。通过将育亨宾提取物溶解于促溶剂之后再与液体制剂的溶剂进行混合，从而提升育亨宾提取物在气溶胶生成系统中的使用量，促进亨宾提取物在气溶胶生成系统中的应用。

Description

液体制剂及其制备方法、气溶胶生成系统、用于气溶胶生成系统的筒以及气溶胶生成装置
本申请要求于2021年10月26日提交中国专利局，申请号为202111248947.0，发明名称为“液体制剂及其制备方法、气溶胶生成系统、用于气溶胶生成系统的筒以及气溶胶生成装置”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本申请涉及雾化技术领域，尤其涉及一种含有育亨宾的液体制剂、液体制剂制备方法及气溶胶生成系统和用于气溶胶生成系统的筒以及气溶胶生成装置。
背景技术
气溶胶生成系统包括气溶胶生成装置，以及储存于气溶胶生成装置内部的液体制剂。气溶胶生成装置通过将液体制剂雾化形成气溶胶。液体制剂主要包括甘油和1，2-丙二醇、以及合成类香精、尼古丁和/或尼古丁盐等。气溶胶生成系统除了作为传统的燃烧类的卷烟产品的替换品之外，还可以作为用于辅助治疗，其主要的方式将保健功效成分添加至液体制剂中，保健功效成分通过雾化的方式形成气溶胶被用户吸食。近年来，大健康产业发展快速，具有保健功效成分的液体制剂来越受到研发人员和消费者的关注，选取对使用者真正有益的保健功效组分添加至液体制剂中，并使得保健功效组分的作用得以发挥更是关注的焦点。
育亨宾树是一种在非洲有着百年历史的草本植物，目前市场上也有众多以育亨宾提取物为原料的保健品。现有技术中，育亨宾提取物常以盐酸育亨宾的形式存在，但是盐酸育亨宾在甘油-丙二醇体系类的液体制剂中的溶解度低，极容易析出，形成浑浊液，从而导致了育亨宾难以转化为气溶胶被使用者吸食，极大阻碍了育亨宾提取物在气溶胶生成系统的使用。
发明内容
为了解决现有技术中的含有育亨宾的液体制剂中的育亨宾组分转化困难的 问题，本申请实施例提供一种用于气溶胶生成系统的液体制剂，所述液体制剂包括育亨宾提取物、促溶剂和溶剂；其中，所述育亨宾提取物在所述促溶剂中的溶解能力大于所述育亨宾提取物在所述溶剂中的溶剂能力；所述育亨宾提取物溶解于所述促溶剂后能够与所述溶剂形成稳定透明的溶液。
在一些实施例中，以所述液体制剂的质量百分比计，所述育亨宾提取物的质量百分比含量为0.01-15％；所述促溶剂的质量百分比含量为0.09-15％；所述溶剂的质量百分比含量为50-99.9％。
在一些实施例中，所述育亨宾提取物包括育亨宾碱。
在一些实施例中，所述育亨宾与所述促溶剂形成育亨宾浓缩液；以所述液体制剂的重量百分比计，所述育亨宾浓缩液的质量百分比含量为0.1～30％。
在一些实施例中，所述溶剂包括甘油和丙二醇。
在一些实施例中，以所述液体制剂的重量百分比计，所述育亨宾提取物的质量百分比含量为0.015-12％；或者，所述育亨宾提取物的质量百分比含量为0.02-12％。
在一些实施例中，所述促溶剂包括苯甲醇和有机酸中的至少一种。
在一些实施例中，所述促溶剂还包括水。
在一些实施例中，所述有机酸包括乳酸、冰乙酸、己二酸、富马酸、酒石酸、苹果酸、柠檬酸和苯甲酸中的至少一种。
在一些实施例中，以所述液体制剂的重量百分比计，所述苯甲醇的质量百分比含量为0-27％；或者，所述苯甲醇的质量百分比含量为0.008-15％；或者，所述苯甲醇的质量百分比含量为0.012-9％。
在一些实施例中，以所述液体制剂的重量百分比计，所述有机酸的质量百分比含量为0-24％；或者，所述有机酸的质量百分比含量为0.008-15％；或者，所述有机酸的质量百分比含量为0.012-9％。
在一些实施例中，以所述液体制剂的重量百分比计，所述水的质量百分比含量为0-24％；或者，所述水的质量百分比含量为0.01-15％；或者，所述水的质量百分比含量为0.02-12％。
在一些实施例中，所述液体制剂还包括被甜味剂、凉味剂和风味组合物中的至少一种。
本申请实施例还提供一种准备上述液体制剂的方法，包括如下步骤：制备育亨宾碱；将育亨宾碱加入促溶剂中，使得育亨宾碱在促溶剂中充分溶解得到育亨宾浓缩液；将育亨宾浓缩液加入溶剂中。
在一些实施例中，所述育亨宾碱由盐酸育亨宾进行酸化处理工艺制备。
本申请还提供一种用于气溶胶生成系统的筒，所述筒容纳有上述液体制剂。
本申请还提供一种气溶胶生成系统，包括上述筒以及气溶胶生成装置，所述气溶胶生成装置被构造成可接收所述筒的至少一部分，以及用于使所述液体制剂雾化形成气溶胶。
本申请实施例还提供一种气溶胶生成装置，包括雾化器和容纳有上述液体制剂的腔室，所述雾化器用于雾化所述液体制剂生成气溶胶。
本申请实施例的有益效果是：上述液体制剂中，通过将育亨宾提取物溶解于促溶剂中，由于育亨宾提取物在促溶剂中的溶解能力大于其在溶剂中的溶解能力，育亨宾提取物溶解于促溶剂后能够与液体制剂中的溶剂形成稳定透明的溶液，从而提升育亨宾提取物在气溶胶生成系统中的使用量，促进亨宾提取物在气溶胶生成系统中的应用。
附图说明
一个或多个实施例通过与之对应的附图中的图片进行示例性说明，这些示例性说明并不构成对实施例的限定，除非有特别申明，附图中的图不构成比例限制。
图1是本申请实施例提供的脱酸工艺处理前后盐酸育亨宾(a)、育亨宾纯碱(b)的HPLC谱图；
图2是本申请实施例提供的盐酸育亨宾、育亨宾纯碱雾化形成的气溶胶的HPLC谱图；
图3是本申请实施例提供的液体制剂a、液体制剂b以及液体制剂c三组溶液的溶解情况对比图；
图4是本申请实施例11提供的四组育亨宾转化率对比图。
具体实施方式
为了便于理解本申请，下面结合附图和具体实施方式，对本申请进行更详细的说明。
育亨宾提取物是从生长于非洲的一种天然植物“YOHIMBE”育亨宾的树皮中提取的活性物质。育亨宾能够作用于性器官，能使性器官血管扩充，增加性器官的血流量，增加一氧化二氮的形成，从而增强性功能。这是目前较为肯定而且应用最多的一种植物性治疗勃起功能障碍的纯植物制剂，并可预防前列腺肥大和泌尿系统感染。将育亨宾提取物添加至气溶胶生成系统所使用的液体制剂中，通过气溶胶生成装置雾化形成气溶胶，用户通过吸食气溶胶，可以使得育亨宾发挥功能疗效。因此，将育亨宾应用于气溶胶生成系统领域，可以极大地扩充气溶胶生成装置的健康使用效果。
育亨宾提取物包括盐酸育亨宾和育亨宾碱。育亨宾碱的化学式为C21H26N2O3，易溶于氯仿，溶解于甲醇、乙醇，微溶于水。市售的育亨宾提取物主要以盐酸育亨宾的形式存在，盐酸育亨宾的化学式为C21H27CLN2O3，易溶于氯仿，溶解于甲醇、乙醇，微溶于水。经过试验发现盐酸育亨宾和育亨宾碱在甘油和丙二醇体系的溶剂中，溶解度都极低，以液体制剂的重量百分比计算，盐酸育亨宾和育亨宾碱的添加量远低于1％时，都会有晶体析出。由于育亨宾提取物难溶解于溶剂中，导致育亨宾难以转化为气溶胶被使用者吸食。
为了促进育亨宾提取物在气溶胶生成系统中的有效应用，本申请实施例1提供一种含有育亨宾提取物的液体制剂，用于气溶胶生成系统。该液体制剂包括溶剂、育亨宾浓缩液。育亨宾提取物存在于育亨宾浓缩液中。育亨宾浓缩液可以与甘油-丙二醇体系的溶剂形成稳定透明的溶液，从而解决育亨宾提取物在甘油-丙二醇体系溶剂中溶解困难的问题。
以液体制剂的重量百分比计，育亨宾浓缩液的质量百分比含量为0.1-30％；溶剂的质量百分比含量为50-99.9％。育亨宾浓缩液中包括育亨宾提取物，以液体制剂的重量计，育亨宾提取物的质量百分比含量为0.01-15％；或者育亨宾提取物的质量百分比含量为0.015-12％；或者育亨宾提取物的质量百分比含量为 0.02-12％。
进一步地，在育亨宾浓缩液中，以育亨宾浓缩液的重量百分比计，育亨宾提取物的质量百分比为10-50％；可选的，育亨宾提取物的质量百分比为15-40％；更进一步地，育亨宾提取物的质量百分比也可以为20-40％。综上，以液体制剂的重量百分比计，育亨宾提取物的质量百分比为0.01-15％；可选的，育亨宾提取物的质量百分比为0.015-12％；进一步地，育亨宾提取物的质量百分比可以为0.02-12％。可选的，育亨宾提取物的具体添加量，可根据用户的需求进行调整，例如，以液体制剂的重量百分比计，育亨宾提取物的质量百分比可以是1％、2％、5％、6％、8％、10％、12％、14％或者是0.01-15％之间的任一个数值。由于育亨宾提取物可以大剂量的溶解于促溶剂中形成育亨宾浓缩液，通过调整育亨宾浓缩液在液体制剂中的配比，就可以任意改变育亨宾提取物在液体制剂中的添加量。
本申请实施1还提供了一部分配制上述液体制剂的具体组分配方，以液体制剂的总量百分比计，各个组分的质量百分比含量，参考如下表1所示。
表1.液体制剂配方
  育亨宾浓缩液 甘油 丙二醇
1 30％ 50％ 20％
2 20％ 60％ 20％
3 10％ 80％ 10％
4 1％ 70％ 29％
5 0.1％ 70％/ 29.9％
育亨宾提取物主要以育亨宾碱的形式存在于该育亨宾浓缩液中。在一些实施方案中，溶剂主要包括甘油、丙二醇，甘油和丙二醇两个组分可以以任意比例混合。在可选的实施方案中，溶剂还可以包括丁二醇，1,2,4-丁三醇，一缩二丙二醇，二甘醇，三甘醇，聚乙二醇200，聚乙二醇400，三醋酸甘油酯，二丙二醇缩醚，乙醇，水，柠檬酸三乙酯，辛癸酸甘油酯中的一种或几种。具体的溶剂选择，需要根据添加至溶剂中的组分的种类进行优化选择。从提高气溶胶生成装置产生的气溶胶的质量的角度考虑，甘油和丙二醇是溶剂中的优选组 分。
由于育亨宾碱的来源有限，在本申请提供的实施例2中，通过将盐酸育亨宾通过脱酸工艺形成育亨宾碱。有机物的脱酸工艺可以通过氧化或者酸碱中和方式进行，其中酸碱中和方式包括酯化反应。现在以酯化反应为例进行具体说明，盐酸育亨宾的脱酸处理工艺主要包括以下几个步骤：
第一步酯化反应；
将盐酸育亨宾粉末加入乙酸乙酯中；待充分溶解后，移入分液漏斗中，加入纯净水，充分震荡分液漏斗，混合均匀，静置等待分层。其中，以重量比计算，盐酸育亨宾与乙酸乙酯的比例为1:(40-70)；以体积比计算，纯净水与乙酸乙酯的比例为1：(2-3)。
第二步调酸碱度并过滤
待溶液分层后形成水层和乙酸乙酯层，其中上层为乙酸乙酯层，下层为水层；加入足够的氢氧化钠溶液，充分震荡分液漏斗，直至混合液的PH值约为9；静置分层后，放出下层的水。
再次加入足够量的纯净水洗涤上层乙酸乙酯层，重复3次。其中，氢氧化钠溶液浓度为2-6mol/L；以体积比计算，纯净水与乙酸乙酯的比例为1：(2-3)。
第三步提纯育亨宾碱
收集上述步骤中的乙酸乙酯层，将混合液放入旋转蒸发仪中，通过减压并旋转蒸发，直至旋转瓶内的液体转化为干燥固体，取出上述粉末状固体即可得到育亨宾碱。
重复步骤三反复提纯，可以制得纯度高于98％(以质量百分比计)的育亨宾碱粉末。
在本申请提供的实施例3中，通过检测对比分析了实施例2中的脱酸处理工艺对育亨宾的功效成分是否产生影响。检测分析方法为：将脱酸工艺处理前的盐酸育亨宾，将脱酸工艺处理后的育亨宾碱分别加入液相色谱仪中，通过液相色谱对比分析，验证脱酸处理工艺对育亨宾的功效成分是否产生影响。如下对液相色谱的对比分析方式进行具体说明：
(1)色谱条件：DGU-20A5R型液相色谱仪，反相色谱柱C18，4.6x250mm，3.5um；流动相：乙腈－水(体积比：30∶70)；柱温35℃，流速为1.0mL/min；检测波长278nm，进样10μL。
(2)将盐酸育亨宾、脱酸处理工艺得到的育亨宾碱加入色谱仪中，进行液相色谱谱分析操作。通过液相色谱对比分析，得到的色谱图参考图1所示，两个色谱图的峰值区间保持一致，上述色谱分析表明本申请实施例2提供的脱酸处理工艺对育亨宾的活性官能团并未产生影响。
在本申请提供的实施例4中，还进一步将脱酸工艺处理前的盐酸育亨宾配制成雾化液体制剂1以及将脱酸工艺处理后的育亨宾碱配制成雾化液体制剂2；将液体制剂1加入气溶胶生成装置中雾化得到气溶胶1，将液体制剂2加入气溶胶生成装置中雾化得到的气溶胶2；并使用液相色谱对比分析气溶胶1和气溶胶2的性能。具体的液相色谱的对比分析方式与上述溶液1和溶液2的相同，参考如下说明：
(1)色谱条件：DGU-20A5R型液相色谱仪，反相色谱柱C18，4.6x250mm，3.5um；流动相：乙腈－水(体积比：30∶70)；柱温35℃，流速为1.0mL/min；检测波长278nm，进样10μL。
(2)分别采集气溶胶1和气溶胶2加入液相色谱仪中，进行液相色谱分析操作。通过液相色谱对比分析，得到的色谱图参考图2所示，两个色谱图的峰值区间大致保持一致，且图2和图1的峰值区间也基本保持一致。上述色谱分析表明气溶胶1中含有育亨宾组分、气溶胶2中含有育亨宾组分，盐酸育亨宾以及育亨宾碱都可以以气溶胶的形式被人体吸收，进一步达到保健功效。需要说明的是，液体制剂1和液体制剂2中均未使用甘油-丙二醇体系的溶剂体系，故盐酸育亨宾和育亨宾碱都可以有效转化为气溶胶。
为了能够最大程度提高育亨宾在丙二醇-甘油体系溶剂中的溶解度，将经过上述脱酸处理工艺得到的育亨宾碱配制成育亨宾浓缩液。在本申请实施例5中提供了育亨宾浓缩液的配方。该育亨宾浓缩液包括育亨宾碱以及促溶剂，其中，育亨宾碱能够充分溶解于促溶剂中，形成稳定透明的溶液，不会产生育亨宾的析出物。促溶剂包括苯甲醇、有机酸和水。其中，苯甲醇和有机酸为作为促溶剂的优选组分。有机酸包括但不限于乳酸、冰乙酸、己二酸、富马酸、苹果酸、 柠檬酸和苯甲酸中的一种或几种混合。有机酸中优选乳酸和冰乙酸。关于育亨宾碱在促溶剂中的溶解机理，一方面，育亨宾碱能够与苯甲醇或者有机酸之间形成分子间氢键，从而促进育亨宾碱在苯甲醇或者有机酸溶剂中的溶解。另一方面，育亨宾碱为极性有机物，苯甲醇、冰乙酸和乳酸等为极性有机溶剂，可以促进苯育亨宾碱在上述两类物质中的溶解。而丙二醇、甘油的极性小于苯甲醇、冰乙酸、水的极性，根据相似相溶原理，极性的育亨宾碱更易溶解于极性较强的苯甲醇、冰乙酸、乳酸以及水混合形成的促溶剂中。
以育亨宾浓缩液的重量百分比计，育亨宾碱的质量百分比为10-50％；可选的，育亨宾碱的质量百分比为15-40％；更进一步地，育亨宾碱的质量百分比也可以为20-40％。在育亨宾浓缩液中，以育亨宾浓缩液的重量百分比计，苯甲醇的质量百分比为0-90％；可选的，苯甲醇的质量百分比为8-50％；更进一步地，苯甲醇的质量百分比也可以为12-30％。在育亨宾浓缩液中，以育亨宾浓缩液的重量百分比计，有机酸的质量百分比为0-80％；可选的，有机酸的质量百分比为8-50％；更进一步地，有机酸的质量百分比也可以为12-30％。在育亨宾浓缩液中，以育亨宾浓缩液的重量百分比计，水的质量百分比为0-80％；可选的，水的质量百分比为10-50％；更进一步地，水的质量百分比也可以为20-40％。可理解的是，促溶剂可选自任何能够促进育亨宾碱或者盐酸育亨宾溶解的有机物，但是促溶剂需要满足气溶胶生成系统的雾化液体制剂的雾化功能要求，在能够形成适于抽吸的气溶胶的同时，不影响液体制剂雾化形成的气溶胶的性能，该性能包括口感、烟雾稳定性以及使用者的健康等。
在液体制剂中，以液体制剂的重量百分比计，苯甲醇的质量百分比为0-27％；可选的，苯甲醇的质量百分比为0.008-15％；可选的，苯甲醇的质量百分比含量为0.012-9％。可理解的是，苯甲醇的具体添加的剂量可以根据需要溶解的育亨宾碱的添加量需求进行适应性调节，苯甲醇的质量比含量可以为0-27％之间的任意一个数值。
在液体制剂中，以液体制剂的重量百分比计，有机酸的质量百分比含量为0-24％；可选的，有机酸的质量百分比含量为0.008-15％；可选的，有机酸的质量百分比含量为0.012-9％。可理解的是，有机酸的具体添加的剂量可以根据需要溶解的育亨宾碱的添加量需求进行适应性调节，有机酸的质量比含量可以为 0-24％之间的任意一个数值。
关于促溶剂在育亨宾浓缩液中的具体含量，可以根据需要添加的育亨宾提取物的含量需求进行适应性调整，而不仅限于上述的含量范围。例如，如果用于气溶胶生产系统的液体制剂中的育亨宾提取物的含量需求为3％(以质量百分比计)，在液体制剂中，育亨宾浓缩液的含量为15％(以质量百分比计)，则在育亨宾浓缩液中，育亨宾提取物的含量为20％(以质量百分比计)，促溶剂的含量为80％(以质量百分比计)。
本申请实施例6中，还提供了上述育亨宾浓缩液的制备工艺，包括如下步骤：
1、称取育亨宾碱粉末，加入苯甲醇溶剂，使得苯甲醇能够充分浸润育亨宾碱粉末；
2、加入纯净水，可以进一步浸润上述溶液中的育亨宾碱粉末；
3、加入冰乙酸至上述溶液中；
4、密封盛装上述溶液的容器，60℃加热搅拌或者涡旋，使得溶液中的育亨宾碱粉末充分溶解；
5、过滤上述溶液中的杂质，得到育亨宾浓缩液。
需要说明的是，在配制育亨宾浓缩液的过程中，各个组分的含量不同，对应的育亨宾碱粉末的溶解情况不同，且使用的育亨宾碱的纯度大于98％，仍含有少许杂质。使用一些配方配制的育亨宾浓缩液，育亨宾碱能够完全溶解，使用一些配方配制的育亨宾浓缩液，育亨宾碱不能够完全溶解，此时在浓缩液中会存在一些微量的悬浮物质或者一些未溶解的晶核，为了得到稳定的育亨宾浓缩液，需要根据配制的浓缩液的情况选择进行步骤5的操作次数，从而充分过滤配制的育亨宾浓缩液中的杂质。
进一步地，本申请实施例5还提供了一部分配制上述育亨宾浓缩液的具体组分配方，参考如下表2。
表2.育亨宾浓缩液配方
  育亨宾纯碱 苯甲醇 水 冰乙酸
1 10％ 90％ / /
2 20％ 80％ / /
3 10％ / 10％ 80％
4 20％ / 40％ 40％
5 25％ / 50％ 25％
6 5％ 5％ 80％ 10％
7 20％ 10％ 50％ 20％
8 30％ 30％ 25％ 15％
9 35％ 27％ 13％ 25％
10 40％ 16％ 28％ 16％
需要说明的是，表1仅列出了配制育亨宾浓缩液的一部分配方，在满足本申请实施例提供的各个组分的质量含量配比的情况下，可以根据具体的育亨宾提取物的浓度需求进行适应性调整。
本申请实施例7还进一步对比分析了将不同的育亨宾提取物添加至甘油-丙二醇体系溶剂中的雾化液的溶解性。具体的分析方法如下所示：
(1)配制液体制剂a：将盐酸育亨宾加入至甘油-丙二醇体系的溶剂中；其中，以液体制剂a的重量计，盐酸育亨宾的质量比含量为2％；并对液体制剂a加热30min，加热温度为60℃；
(2)配制液体制剂b：将上述实施例2脱酸处理工艺得到的育亨宾碱加入至甘油-丙二醇体系的溶剂中；其中，以液体制剂b的重量计，育亨宾碱的质量比含量为2％；并对液体制剂b加热30min，加热温度为60℃；
(3)配制液体制剂c：将本申请实施例5提供的育亨宾浓缩液加入至甘油-丙二醇体系的溶剂中；其中，以液体制剂c的重量计，育亨宾碱的质量百分比含 量为2％；并对液体制剂c加热30min，加热温度为60℃。
观察液体制剂a、液体制剂b以及液体制剂c三组溶液的溶解情况，得到三组溶液的溶解状态参考表2和图3所示。
表3.不同育亨宾原料的溶解状态
名称 液体制剂a 液体制剂b 液体制剂c
溶解状态 无法溶解 无法溶解 溶液透明
参考表3和图3所示，液体制剂a和液体制剂b溶液浑浊，表明盐酸育亨宾在甘油-丙二醇体系溶剂中溶解度很小，进过脱酸处理工艺配制的育亨宾碱在甘油-丙二醇体系溶剂中溶解度也很小；而液体制剂c溶液澄清透明，且该液体制剂c放置一段时间后观察，溶液c仍是透明的，无晶体析出，表明本申请实施例5提供的育亨宾浓缩液在甘油-丙二醇体系的溶剂中能够形成稳定透明的溶液体系。通过将育亨宾配制成育亨宾浓缩液可以解决其在液体制剂中的添加问题，可以根据具体使用的需求增加育亨宾提取物的添加量，同时配制的雾化液体制剂稳定性好，无沉淀析出。
本申请实施例9进一步对比分析含有不同的育亨宾提取物的液体制剂在气溶胶生成装置中转化为气溶胶的育亨宾的转化率效果。准备两组含有育亨宾提取物的液体制剂，分别为液体制剂3和液体制剂4，液体制剂3在气溶胶生成装置中雾化形成气溶胶3，液体制剂4在气溶胶生成装置中雾化形成气溶胶4。
液体制剂3使用盐酸育亨宾添加至甘油-丙二醇体系溶剂中配制，以液体制剂3的重量百分比计算，盐酸育亨宾的质量百分比为1％，丙二醇的质量百分比为49％，甘油的质量百分比为50％。
液体制剂4使用育亨宾浓缩液添加至甘油-丙二醇体系溶剂中配制，以液体制剂4的重量百分比计算，育宾亨浓缩液的质量百分比含量为30％，丙二醇的质量百分比为20％,甘油的质量百分比为50％。其中，在液体制剂4使用的育亨宾浓缩液中，以育亨宾浓缩液的重量计算，育亨宾碱的质量百分比含量为3.33％，通过计算可得，以液体制剂4的重量计算，育亨宾碱的质量百分比含量为1％。
本申请实施例10提供了一种用于气溶胶生成系统的气溶胶生成装置，气溶 胶生成装置包括具有雾化功能的雾化器。雾化器包括加热元件和导液元件。导液元件可以吸收和传递液体制剂，加热元件可以将液体制剂雾化形成气溶胶。按照导液元件所使用的材料以及雾化器的制备工艺的不同，雾化器包括陶瓷芯雾化器，以及棉芯雾化器。在棉芯雾化器中，导液元件可以由具有毛细结构的储液性能优异的材料制备，如无纺布、棉等。加热元件可以由不锈钢、镍铬合金、铁铬铝合金、金属钛等材质中的至少一种制成的螺旋状发热丝或者发热网；导液元件可以固定设置于螺旋状发热丝或者发热网的外部；或者，螺旋状发热丝或者发热网围绕导液元件的至少部分表面设置。在陶瓷芯雾化器中，导液元件可以由多孔陶瓷、多孔玻璃陶瓷或多孔玻璃等硬质毛细结构制成的多孔体结构，导液元件大致呈块状，在导液元件的至少部分表面上固定有加热元件。加热元件可以是发热涂层、发热片或发热网的一种。其中，发热涂层可以包括但不限于电磁感应发热涂料和红外感应发热涂料等。或者，加热元件可以采用具有导电性的原材料粉末与印刷助剂混合成浆料后于印刷后烧结于多孔体表面上。本申请实施例9中进一步对比分析了陶瓷雾化器和棉芯雾化器对液体制剂中育亨宾转化率的影响。
本申请实施例9测试分析气溶胶3和气溶胶4中的育亨宾转化率，所使用的测试方法参考如下说明：
测试方法包括如下步骤：用抽烟机按照国际标准对液体制剂3和液体制剂4分别进行抽吸测试。具体的抽吸测试条件为：每次抽吸时间为3秒，抽吸时间间隔为30秒，抽吸次数为50次，每次抽吸的液体制剂的量为55mL。用剑桥滤片分别收集气溶胶3和气溶胶4。使用有机溶剂萃取气溶胶3的盐酸育亨宾，过滤得到盐酸育亨宾；使用有机溶剂萃取气溶胶4中的育亨宾碱，过滤得到育亨宾碱，用液相色谱分析方法并按照如下转化率的计算公式，分别计算得到液体制剂3中的盐酸育亨宾雾化形成的气溶胶3中的盐酸育亨宾的转化率，以及液体制剂4中的育亨宾碱雾化形成的气溶胶4中的育亨宾碱的转化率。
转化率计算公式：
Figure PCTCN2022126035-appb-000001
其中C 0＝m 0/V，C 1＝m 1/V。
上述转化率的计算公式中：W％为育亨宾转化效率；C 0为剑桥滤片捕集的气溶胶浓度；C 1为液体制剂的浓度；A 0为气溶胶中的育亨宾的色谱峰面积；A 1为液体 制剂中的育亨宾的色谱峰面积；m 0为气溶胶质量(即剑桥滤片捕集前后质量差)；m 1为液体制剂的质量；V为萃取溶剂的体积。
在本申请提供的实施例9中，将液体制剂3分别加入相同规格的配备有棉芯雾化器的气溶胶生成装置1、相同规格的配备有陶瓷雾化器的气溶胶生成装置2；将液体制剂4分别加入相同规格的配备有棉芯雾化器的气溶胶生成装置3、相同规格的配备有陶瓷雾化器的气溶胶生成装置4中。然后分别将上述气溶胶生成装置1、气溶胶生成装置2、气溶胶生成装置3、气溶胶生成装置4连接至同一抽烟机，按照上述抽吸测试方法分别得到第一组气溶胶、第二组气溶胶、第三组气溶胶以及第四组气溶胶。然后分别使用同一种有机溶剂萃取第一组气溶胶中的盐酸育亨宾样品1、使用同一种有机溶剂萃取第二组气溶胶的盐酸育亨宾样品2、使用同一种有机溶剂萃取第三组气溶胶中的育亨宾碱样品3、使用同一种有机溶剂萃取第四组气溶胶中的育亨宾碱样品4。然后分别将样品1、样品2、样品3和样品4加入液相色谱分析仪中，进行液相色谱分析得到样品1的育亨宾的色谱峰面积为A 01、得到样品2的育亨宾的色谱峰面积为A 02、得到样品3的育亨宾的色谱峰面积为A 03、以及得到样品4的育亨宾的色谱峰面积为A 04。
准备液体制剂3和液体制剂4，其中液体制剂3的质量为m 13，液体制剂4的质量为m 14。分别将上述液体制剂3和液体制剂4加入液相色谱仪中进行液相色谱分析操作，得到液体制剂3中的的育亨宾对应的色谱峰面积为A 13，得到液体制剂4中的育亨宾对应的色谱峰面积为A 14。
然后将A 01和A 13带入上述转化率的计算公式，得出盐酸育亨宾液体制剂在配备有棉芯雾化器的气溶胶生成装置1中雾化形成的第一组气溶胶中盐酸育亨宾的转化效率；将A 02和A 13带入上述转化率的计算公式，得出盐酸育亨宾液体制剂在配备有陶瓷芯雾化器的气溶胶生成装置2中雾化形成的第二组气溶胶中盐酸育亨宾的转化效率；将A 03和A 14带入上述转化率的计算公式，得出育亨宾浓缩液液体制剂在配备有棉芯雾化器的气溶胶生成装置3中雾化形成的第三组气溶胶中育亨宾碱的转化效率；将A 04和A 14带入上述转化率的计算公式，得出育亨宾浓缩液液体制剂在配备有陶瓷芯雾化器的气溶胶生成装置4中雾化形成的第四组气溶胶中育亨宾碱的转化效率。
最后，四组分析对比试验的结果参考图4所示，从图中可以看出，在配备有 陶瓷芯的气溶胶生成装置中，与图4中的雾化装置1对应，盐酸育亨宾液体制剂雾化形成的气溶胶中，育亨宾转化率为51％，育亨宾浓缩液液体制剂雾化形成的气溶胶中，育亨宾的转化率为81％，即使用本申请实施例提供的育亨宾浓缩工艺配备的液体制剂，可以显著提高气溶胶中的育亨宾的含量。在配备有棉芯的气溶胶生成装置中，与图4中的雾化装置2对应，盐酸育亨宾液体制剂雾化形成的气溶胶中，育亨宾的转化率为36％，育亨宾浓缩液液体制剂雾化形成的气溶胶中，育亨宾的转化率为56％，即使用本申请实施例提供的育亨宾浓缩工艺配备的液体制剂，可以显著提高气溶胶中的育亨宾的含量。同样的含有育亨宾的液体制剂中，使用配备有陶瓷雾化器的气溶胶生成装置进行雾化形成的气溶胶中的育亨宾的含量为N1，使用配备有棉芯雾化器的气溶胶生成装置进行雾化形成的气溶胶中的育亨宾的含量为N2，N1>N2。故配备有陶瓷芯雾化器的气溶胶生成装置对含有育亨宾的液体制剂的雾化效果更好，能提高育亨宾的转化率。
本申请实施例11还提供一种含有育亨宾的液体制剂，用于气溶胶生成系统。液体制剂包括育亨宾浓缩液、溶剂、甜味剂、凉味剂和风味组合物。以液体制剂的重量计，育亨宾浓缩液的质量百分比含量为0.1-30％；溶剂的质量百分比含量为50-99.9％；甜味剂的质量百分比含量为0.01-0.5％；凉味剂的质量百分比含量为0.01-8％；风味组合物的质量百分比含量为0.01-15％。
在本申请实施例11提供的液体制剂中，溶剂包含但不限于丙二醇、甘油、丁二醇、1,2,4-丁三醇、一缩二丙二醇、二甘醇、三甘醇、聚乙二醇200、聚乙二醇400、三醋酸甘油酯、二丙二醇缩醚、乙醇、水、柠檬酸三乙酯和辛癸酸甘油酯中的一种或几种的混合。
在本申请实施例11提供的液体制剂中，凉味剂包含但不限于薄荷脑、薄荷酮、异薄荷酮、WS-23(2-异丙基-N,2,3-三甲基丁酰胺)、WS-3(N-乙基-对薄荷基-3-甲酰胺)、WS-5(N-(乙氧羰基甲基)-对烷-3-甲酰胺)、乳酸薄荷酯和薄荷酮甘油缩醛中的一种或几种的组合，总添加量为0.01％-8％(以质量百分比含量计)。
在本申请实施例11提供的液体制剂中，甜味剂包含但不限于纽甜、甜蜜素、三氯蔗糖、阿斯巴甜、甜菊糖苷和安赛蜜中的一种或几种的组合，总添加量为0.01-0.5％(以质量百分比含量计)。
在本申请实施例11提供的液体制剂中，风味组合物为天然或合成香精香料，包括但不限于水果、花香、茶香、薄荷、咖啡、汽水、糖果或烟草等口味。添加风味组合物可用于丰富液体制剂雾化形成的气溶胶的口感。
本申请实施例12还提供了一种气溶胶生成装置，该气溶胶生成装置配备有可容纳本申请的任一实施例提供的液体制剂的筒，所述液体制剂中含有育亨宾提取物。气溶胶生成装置内部设有可将液体制剂雾化形成气溶胶的雾化器以及能够使得气溶胶稳定释放的控制模块，该雾化器可经由电源驱动进行雾化，并通过气溶胶生成装置内部的气溶胶输出通道输出至气溶胶生成装置外部供使用者吸食。除了电驱动雾化外，气溶胶生成装置也可通过其他的形式将液体制剂雾化形成气溶胶从而有效传递给使用者，可根据气溶胶生成装置的筒内部的液体基质的具体组分的雾化温度进行优化选择，具体的雾化形式不作限定。在一些实施方案中，气溶胶生成装置可由电阻和/或电磁的发热体进行雾化；在另外的实施方案中，可为超声雾化，或者电加热雾化与超声雾化同时进行；在一些实施方案中，气溶胶生装置也可为空气压缩式雾化装置或按压式喷雾装置。
需要说明的是，本申请的说明书及其附图中给出了本申请的较佳的实施例，但并不限于本说明书所描述的实施例，进一步地，对本领域普通技术人员来说，可以根据上述说明加以改进或变换，而所有这些改进和变换都应属于本申请所附权利要求的保护范围。

Claims (18)

  1. 一种用于气溶胶生成系统的液体制剂，其特征在于，所述液体制剂包括育亨宾提取物、促溶剂和溶剂；
    其中，所述育亨宾提取物在所述促溶剂中的溶解能力大于所述育亨宾提取物在所述溶剂中的溶解能力，所述育亨宾提取物溶解于所述促溶剂后能够与所述溶剂形成稳定透明的溶液。
  2. 如权利要求1所述的液体制剂，其特征在于，以所述液体制剂的质量百分比计，所述育亨宾提取物的质量百分比含量为0.01-15％，所述促溶剂的质量百分比含量为0.09-15％，所述溶剂的质量百分比含量为50-99.9％。
  3. 如权利要求1或2所述的液体制剂，其特征在于，所述育亨宾提取物包括育亨宾碱。
  4. 如权利要求1所述的液体制剂，其特征在于，所述育亨宾与所述促溶剂形成育亨宾浓缩液；
    以所述液体制剂的重量百分比计，所述育亨宾浓缩液的质量百分比含量为0.1～30％。
  5. 如权利要求1或2所述的液体制剂，其特征在于，所述溶剂包括甘油和丙二醇。
  6. 如权利要求3所述的液体制剂，其特征在于，以所述液体制剂的重量百分比计，所述育亨宾提取物的质量百分比含量为0.015-12％，或者所述育亨宾提取物的质量百分比含量为0.02-12％。
  7. 如权利要求1或2所述的液体制剂，其特征在于，所述促溶剂包括苯甲醇和有机酸中的至少一种。
  8. 如权利要求7所述的液体制剂，其特征在于，所述促溶剂还包括水。
  9. 如权利要求7所述的液体制剂，其特征在于，所述有机酸包括乳酸、冰乙酸、己二酸、富马酸、酒石酸、苹果酸、柠檬酸和苯甲酸中的至少一种。
  10. 如权利要求7所述的液体制剂，其特征在于，以所述液体制剂的重量 百分比计，所述苯甲醇的质量百分比含量为0-27％；
    或者，所述苯甲醇的质量百分比含量为0.008-15％；
    或者，所述苯甲醇的质量百分比含量为0.012-9％。
  11. 如权利要求7所述的液体制剂，其特征在于，以所述液体制剂的重量百分比计，所述有机酸的质量比分含量为0-24％；
    或者，所述有机酸的质量百分比含量为0.008-15％；
    或者，所述有机酸的质量百分比含量为0.012-9％。
  12. 如权利要求8所述的液体制剂，其特征在于，以所述液体制剂的重量百分比计，所述水的质量百分比含量为0-24％；
    或者，所述水的质量百分比含量为0.01-15％；
    或者，所述水的质量百分比含量为0.02-12％。
  13. 如权利要求1所述的液体制剂，其特征在于，所述液体制剂还包括甜味剂、凉味剂和风味组合物中的至少一种。
  14. 一种制备权利要求1-13任一项所述的液体制剂的方法，其特征在于，包括如下步骤：
    制备育亨宾碱；
    将育亨宾碱加入促溶剂中，使得育亨宾碱在促溶剂中充分溶解得到育亨宾浓缩液；
    将育亨宾浓缩液加入溶剂中。
  15. 如权利要求14所述的制备液体制剂的方法，其特征在于，所述育亨宾碱由盐酸育亨宾进行脱酸处理工艺制备。
  16. 一种用于气溶胶生成系统的筒，其特征在于，所述筒容纳有液体制剂，所述液体制剂包括如权利要求1-13任一项所述的液体制剂。
  17. 一种气溶胶生成系统，其特征在于，所述气溶胶生成系统包括如权利要求16所述的筒和气溶胶生成装置；
    所述气溶胶生成装置被构造成可接收所述筒的至少一部分，以及用于使所述液体制剂雾化形成气溶胶。
  18. 一种气溶胶生成装置，其特征在于，所述气溶胶生成装置包括雾化器和容纳有如权利要求1-13任一项所述的液体制剂的腔室，所述雾化器用于雾化所述液体制剂生成气溶胶。
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