Aerosol inhalation preparation based on traditional Chinese medicine ingredients and application of aerosol inhalation preparation to substitute tobacco products

Abstract

The invention discloses an aerosol inhalation preparation based on traditional Chinese medicine components and an application of the aerosol inhalation preparation in replacement of tobacco products. The aerosol inhalation preparation comprises a lung clearing group, an aerosol inhalation group and an aerosol inhalation group, wherein the lung clearing group comprises herba houttuyniae extract, folium mori flavone and total anthraquinone of semen cassiae; a qi tonifying group: ginseng extract and cordycepin; the kidney tonifying group comprises cistanche polysaccharide and eucommia total glycoside; a spleen tonifying and blood circulation promoting group: pachymaran and tanshinone; the tranquilizing and sedating group comprises agilawood volatile oil and lily saponin; an atomization carrier: plant glycerin and propylene glycol; the flavoring agent comprises menthol and glycyrrhizic acid. The invention relates to the technical crossing field of traditional Chinese medicines and modern inhalation preparations. According to the aerosol inhalation preparation containing the traditional Chinese medicine components and the application of the aerosol inhalation preparation in replacing tobacco products, through traditional Chinese medicine compound compatibility and a nanometer wrapping technology, the natural aerosol preparation which has the functions of efficient smoking cessation (the smoking desire is reduced by 78% in 24 hours), lung function repair (IL-6 is reduced by 42%) and good taste acceptability (accepted by 92%) is provided, the lung deposition rate of the aerosol inhalation preparation reaches 65%, and the aerosol inhalation preparation is excellent in stability; and a safe and effective solution is provided for tobacco replacement.

Description

Technical Field

[0001] This invention relates to the intersection of traditional Chinese medicine and modern inhalation formulation technology, specifically to a nebulized inhalation formulation based on traditional Chinese medicine ingredients and its application in alternative tobacco products. Background Technology

[0002] Pain points of existing technology; Traditional nicotine replacement therapies (such as patches and chewing gum) have side effects such as palpitations and skin allergies, and cannot simulate smoking behavior, resulting in low user compliance.

[0003] E-cigarettes rely on chemically synthesized ingredients (such as propylene glycol), and long-term use may induce respiratory inflammation. Furthermore, flavorings pose safety risks.

[0004] Existing Chinese medicine smoking cessation products are mostly limited to oral or patch-based administration, which have slow onset of action, low bioavailability, and lack a mechanism design for synergistic regulation of the lungs and kidneys. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a nebulized inhalation formulation based on traditional Chinese medicine ingredients and its application in tobacco alternatives. This solves the problems of traditional nicotine replacement therapies (such as patches and chewing gum) having side effects such as palpitations and skin allergies, failing to simulate smoking behavior, resulting in low user compliance, relying on chemically synthesized ingredients (such as propylene glycol) for e-cigarettes which may induce respiratory inflammation with long-term use, and posing safety risks to flavoring agents. Furthermore, existing traditional Chinese medicine smoking cessation products are mostly limited to oral or patch formulations, have slow onset of action, low bioavailability, and lack a mechanism design for synergistic regulation of the lungs and kidneys.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a nebulized inhalation formulation based on traditional Chinese medicine ingredients, comprising the following raw materials in parts by weight: Lung-clearing group: 10-15 parts of houttuynia cordata extract, 5-8 parts of mulberry leaf flavonoids, and 4-6 parts of total anthraquinones from cassia seed; Qi-tonifying group: 5-10 parts ginseng extract, 2-5 parts cordycepin; Kidney-tonifying group: 3-8 parts of Cistanche deserticola polysaccharide and 3-5 parts of Eucommia ulmoides total glycosides; Spleen-strengthening and blood-activating group: 5-10 parts of Poria polysaccharide, 2-4 parts of Tanshinone; Calming and tranquilizing group: 1-3 parts agarwood volatile oil, 2-4 parts lily saponins; Atomizing carrier: 30-50 parts vegetable glycerin, 10-20 parts propylene glycol; Flavoring agents: 0.5-1 part menthol, 0.2-0.5 part glycyrrhizic acid.

[0007] Preferably, the houttuynia cordata extract is prepared by water extraction, with a total flavonoid content ≥40%; the total glycosides of eucommia are extracted by ultrasonic-assisted extraction with 70% ethanol, with a glycoside purity ≥80%; and the total anthraquinones of cassia seed are prepared by alcohol extraction, with an anthraquinone content ≥60%.

[0008] Preferably, the cordycepin and agarwood volatile oil are encapsulated using liposome technology. The liposomes are composed of soybean lecithin and cholesterol in a mass ratio of 4:1, with a particle size of 50-100 nm and an encapsulation rate of ≥85%. The mulberry leaf flavonoids and poria cocos polysaccharides are encapsulated in chitosan-sodium alginate microspheres with a particle size of 100-200 nm and a sustained release time of ≥6 hours.

[0009] Preferably, the mass ratio of vegetable glycerol to propylene glycol in the atomizing carrier is 3:1 to 5:1, and the viscosity after mixing is 50-80 mPa·s (measured at 25°C).

[0010] Preferably, the formulation has a pH value of 6.8-7.4, a droplet size of 1-5 μm after atomization, and a lung deposition rate of ≥65%.

[0011] This invention discloses a method for preparing a nebulized inhalation formulation, comprising the following steps: (1) Segmented extraction: Houttuynia cordata, mulberry leaf and Poria cocos were extracted by water extraction and refluxed twice at 80℃; Cassia seed, Eucommia bark, and Salvia miltiorrhiza were extracted using 70% ethanol via ultrasonic extraction; Agarwood and Cistanche deserticola were extracted using supercritical CO2 extraction. (2) Nano-encapsulation: Lipid-soluble components (cordycepin, agarwood volatile oil) are encapsulated by liposomes; water-soluble components (mulberry leaf flavonoids, poria polysaccharide) are encapsulated by chitosan-sodium alginate microspheres; (3) Mixing and shaping: Mix each component with the atomizing carrier and flavoring agent, homogenize and emulsify, and then sterilize and fill through a 0.22μm filter membrane.

[0012] Preferably, the supercritical CO2 extraction conditions are: pressure 25-30 MPa, temperature 40-45℃, CO2 flow rate 20-25 L / h, and extraction time 2-3 hours.

[0013] This invention also discloses the application of a nebulized inhalation formulation in tobacco alternatives, with a daily inhalation dose of 0.5-2 mL, used continuously for 4-8 weeks, to reduce anxiety behavior during nicotine withdrawal (serum corticosterone returns to normal levels ≥90%); inhibit the expression of inflammatory factors IL-6 and TNF-α in lung tissue (reduction ≥40%); and improve blood rheological parameters (whole blood viscosity decreases ≥15%).

[0014] Preferably, the formulation needs to be used in conjunction with a low-temperature ceramic core atomizing device, with the atomization temperature controlled at 120-150℃ to avoid pyrolysis of the components.

[0015] Preferably, the mass ratio of Houttuynia cordata extract to total eucommia ulmoides glycosides in the formula is (10-15):(3-5), and the two work synergistically to reduce the MDA level in lung tissue (reduction ≥35%).

[0016] This invention provides a nebulized inhalation formulation based on traditional Chinese medicine ingredients and its application in tobacco alternatives. Compared with existing technologies, it has the following advantages: 1. This nebulized inhalation preparation based on traditional Chinese medicine ingredients and its application in tobacco alternatives, through the combination of traditional Chinese medicine compound formulation and nano-encapsulation technology, provides a natural nebulized preparation that combines highly effective smoking cessation (78% reduction in smoking urges within 24 hours), lung function repair (42% reduction in IL-6), and good taste acceptance (92% approval rate). Its lung deposition rate reaches 65% and its stability is excellent, providing a safe and effective solution for tobacco substitution. Attached Figure Description

[0017] Figure 1 This is a schematic diagram illustrating the triple synergistic mechanism of the lung-clearing, kidney-tonifying, and spleen-strengthening effects of the present invention; Figure 2 This is a schematic diagram of the transmission electron microscope structure of the nanoliposomes of the present invention; Figure 3 This is a schematic diagram illustrating the behavioral comparison of rats in the nicotine withdrawal model of this invention. Figure 4 This is a schematic diagram of the in vitro release rate comparison curve of the present invention; Figure 5 This is a schematic diagram showing the mass ratio of the core components of this invention. Detailed Implementation

[0018] The technical solutions in the embodiments of the present invention have been clearly and completely described. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0019] Please see Figure 1-5 This invention provides a technical solution: a nebulized inhalation preparation based on traditional Chinese medicine ingredients is composed of the following raw materials in parts by weight: Lung-clearing group: 10-15 parts of houttuynia cordata extract, 5-8 parts of mulberry leaf flavonoids, and 4-6 parts of total anthraquinones from cassia seed; Qi-tonifying group: 5-10 parts ginseng extract, 2-5 parts cordycepin; Kidney-tonifying group: 3-8 parts of Cistanche deserticola polysaccharide and 3-5 parts of Eucommia ulmoides total glycosides; Spleen-strengthening and blood-activating group: 5-10 parts of Poria polysaccharide, 2-4 parts of Tanshinone; Calming and tranquilizing group: 1-3 parts agarwood volatile oil, 2-4 parts lily saponins; Atomizing carrier: 30-50 parts vegetable glycerin, 10-20 parts propylene glycol; Flavoring agents: 0.5-1 part menthol, 0.2-0.5 part glycyrrhizic acid.

[0020] The application of a nebulized inhalation formulation based on traditional Chinese medicine ingredients in the preparation of alternative tobacco products. The drug is delivered by nebulized inhalation, with a daily dose of 0.5-2 mL, and is used to relieve nicotine withdrawal symptoms, repair alveolar epithelial damage, reduce serum inflammatory factor levels, and improve blood viscosity.

[0021] A method for preparing atomized inhalation based on traditional Chinese medicine ingredients includes the following steps: Raw material pretreatment Houttuynia cordata extract (water extraction method) Take the dried whole herb of Houttuynia cordata, grind it to 40 mesh, add pure water at a material-to-liquid ratio of 1:15, and reflux extract twice at 80℃ for 1.5 hours each time; combine the filtrates, concentrate under reduced pressure to a relative density of 1.25 (measured at 60℃), and spray dry to obtain a light yellow powder (total flavonoid content ≥40%).

[0022] Mulberry leaf flavonoids (commercially available standardized extract) Purchase total flavonoids from mulberry leaves directly (HPLC detection content ≥80%) for future use.

[0023] Total anthraquinones from Cassia seed (alcohol extraction method) Take cassia seeds, grind them to 60 mesh, add 70% ethanol at a material-to-liquid ratio of 1:8, and extract with ultrasonic assistance (300W power, 40kHz frequency) 3 times, 30 minutes each time; combine the extracts, recover the ethanol under reduced pressure, purify with macroporous resin (model D101), elute with 60% ethanol, concentrate and dry to obtain orange-red powder (total anthraquinone content ≥60%).

[0024] Ginseng extract (water extraction method) Take ginseng root slices, add pure water at a material-to-liquid ratio of 1:10, and reflux at 90℃ for 3 times, 2 hours each time; combine the filtrates, concentrate and freeze dry to obtain a light yellow powder (ginsenoside Rg1 content ≥5%).

[0025] Cordycepin (liposome encapsulated) Soybean phospholipids and cholesterol (4:1) were dissolved in chloroform, cordycepin (dissolved in anhydrous ethanol) was added, and the mixture was rotary evaporated to form a film. Phosphate buffer (pH 7.4) was added, and the mixture was hydrated and then sonicated (200W power, 5 minutes). The mixture was then filtered through a 0.22μm filter membrane to obtain liposomes with a particle size of 80±10nm (encapsulation efficiency ≥85%).

[0026] Cistanche deserticola polysaccharide (supercritical CO2 extraction) The dried stems of Cistanche deserticola were pulverized to 30 mesh and extracted in a supercritical CO2 device (pressure 25 MPa, temperature 40℃, CO2 flow rate 20 L / h) for 2 hours. The extract was collected and freeze-dried to obtain a white polysaccharide powder (purity ≥90%).

[0027] Total glycosides from Eucommia ulmoides (alcohol extraction method) Take the bark of Eucommia ulmoides, pulverize it to 60 mesh, add 70% ethanol at a material-to-liquid ratio of 1:10, and extract with ultrasonic assistance (power 300W, frequency 40kHz) 3 times, 30 minutes each time; combine the extracts, recover the ethanol under reduced pressure, purify with macroporous resin (model AB-8), elute with 60% ethanol, concentrate and dry to obtain a brown powder (total glycosides content ≥80%).

[0028] Poria polysaccharide (water extraction method) Take Poria cocos pieces, crush them to 40 mesh, add pure water at a material-to-liquid ratio of 1:12, and reflux extract twice at 100℃ for 2 hours each time; combine the filtrates, concentrate and precipitate with ethanol (final concentration 80%), centrifuge to collect the precipitate, and vacuum dry to obtain a white powder (polysaccharide content ≥85%).

[0029] Tanshinone (alcohol extraction method) Take the root of Salvia miltiorrhiza, crush it to 50 mesh, add 95% ethanol at a material-to-liquid ratio of 1:8, and reflux at 80℃ for 3 times, 1 hour each time; combine the extracts, concentrate under reduced pressure to a paste, and purify by silica gel column chromatography (eluent: chloroform-methanol=9:1) to obtain red crystals (tanshinone IIA content ≥90%).

[0030] Agarwood volatile oil (supercritical CO2 extraction) Agarwood chips were extracted for 3 hours in a supercritical CO2 device (pressure 30 MPa, temperature 45℃, CO2 flow rate 25 L / h); the volatile oil was collected and dehydrated with anhydrous sodium sulfate to obtain a pale yellow oily substance (β-caryophyllene content ≥70%).

[0031] Lily saponins (water extraction method) Take lily bulbs, crush them to 40 mesh, add pure water at a material-to-liquid ratio of 1:10, and reflux extract twice at 90℃ for 2 hours each time; combine the filtrates, concentrate them, and purify them with macroporous resin (model HPD-100), elute with 50% ethanol, and dry to obtain a white powder (total saponin content ≥60%).

[0032] Vegetable glycerin (commercially available pharmaceutical grade) Pharmaceutical-grade vegetable glycerin (purity ≥99.5%) is purchased directly, requiring no pretreatment.

[0033] Propylene glycol (commercially available pharmaceutical grade) Purchase pharmaceutical-grade propylene glycol (purity ≥ 99.9%) directly for future use.

[0034] Menthol (commercially available crystals) Purchase menthol crystals (purity ≥98%), crush them to 100 mesh, and set aside.

[0035] Glycyrrhizic acid (ethanol extraction method) Take licorice root, grind it to 50 mesh, add 50% ethanol at a material-to-liquid ratio of 1:8, reflux extract at 70℃ 3 times, 1 hour each time; combine the extracts, concentrate under reduced pressure, adjust pH to 3.0, precipitate out, centrifuge and dry to obtain glycyrrhizic acid (purity ≥95%).

[0036] II. Preparation Process (Complete Steps) Raw material premixing Mixing of water-soluble components: Dissolve 12g of houttuynia cordata extract, 6g of mulberry leaf flavonoids, 8g of poria cocos polysaccharide, and 8g of ginseng extract in 40mL of vegetable glycerin and stir at 60℃ until completely dissolved. Mixing of alcohol-soluble components: Mix 5g of total anthraquinones from Cassia tora seeds, 4g of total glycosides from Eucommia ulmoides, and 3g of tanshinone with 10mL of propylene glycol and disperse by ultrasonication (40kHz, 10 minutes). Nano-encapsulated component integration Add cordycepin liposomes (3g) and Cistanche deserticola polysaccharide (5g) to an alcohol-soluble mixture and stir magnetically for 30 minutes. Mulberry leaf flavonoids (6g) and chitosan-sodium alginate microspheres (embedded at a mass ratio of 1:2) were dispersed in 5mL of pure water and ultrasonically treated (100W, 5 minutes) to form a homogeneous suspension. Volatile ingredient addition Agarwood volatile oil (2g), lily saponins (3g), menthol (0.8g), and glycyrrhizic acid (0.3g) were added in sequence, and emulsified using a high-pressure homogenizer (100MPa pressure, 3 cycles) to form a stable emulsion. Final product molding The above mixture was sterilized by passing it through a 0.22μm polyethersulfone filter membrane and then filled into an aluminum aerosol can under nitrogen protection, with a sealing pressure of 0.3MPa. The finished aerosol solution had a pH of 6.8-7.4 and an aerosol particle size of 1-5μm (measured by a laser particle size analyzer).

[0037] The stability test data are shown in Table 1 below;

[0038] Table 1: Stability test (stored at 25℃ for 6 months) III. Key Process Parameters Extraction process Water extraction temperature: 80-100℃, to avoid high temperatures damaging heat-sensitive components (such as mulberry leaf flavonoids); Supercritical CO2 extraction: pressure 25-30MPa, temperature 40-45℃, precisely controlling the yield of volatile oils.

[0039] Nano-encapsulation technology Liposome encapsulation efficiency ≥85%, particle size 50-100nm (verified by dynamic light scattering method); Chitosan-sodium alginate microspheres have a sustained release time of ≥6 hours (in vitro release rate test).

[0040] Sterilization and stability Sterilization is achieved using a 0.22μm filter membrane to avoid component degradation caused by high-temperature sterilization; The finished product retains ≥95% of its active ingredients after being stored at 25°C for 6 months (HPLC verification).

[0041] The experimental data for verifying the synergistic effect of the formulation are shown in Table 2 below;

[0042] Table 2: Validation of the synergistic effect of the formulation (in vitro cell model) Note: p < 0.05 compared to the single-use group; blood viscosity is whole blood high-shear viscosity (200 s⁻¹).

[0043] IV. Examples and Effect Verification Example 1: Preparation of 100mL atomizing fluid Formula: 12g Houttuynia cordata extract, 6g mulberry leaf flavonoids, 5g total anthraquinones from cassia seed, 8g ginseng extract, 3g cordycepin liposomes, 5g Cistanche deserticola polysaccharide, 4g total glycosides from Eucommia ulmoides, 8g Poria cocos polysaccharide, 3g tanshinone, 2g agarwood volatile oil, 3g lily saponins, 40mL vegetable glycerin, 10mL propylene glycol, 0.8g menthol, and 0.3g glycyrrhizic acid.

[0044] Effect verification: In vitro release: ≥90% release rate of active ingredients within 3 hours; Animal experiments: Nicotine withdrawal rats showed a 68% reduction in anxiety behavior and a 42% decrease in IL-6 in lung tissue; Sensory evaluation: 89% of users felt that the taste was close to that of traditional tobacco and that there was no throat irritation.

[0045] The experimental data of the human sensory test results are shown in Table 3 below;

[0046] Table 3: Results of Human Sensory Testing (n=80) Test method: Double-blind randomized trial, subjects inhaled 1 mL daily for 7 days.

[0047] The experimental data of the animal model are shown in Table 4 below;

[0048] Table 4: Behavioral and biochemical indicators of animal models (nicotine withdrawal rats) Note: p < 0.01 compared to the model group (t-test); data were collected from test results after 14 days of continuous treatment (n=10).

[0049] The experimental data of the sensory test results are shown in Table 5 below;

[0050] Table 5: Results of Human Sensory Testing (n=80) Test method: Double-blind randomized trial, subjects inhaled 1 mL daily for 7 days.

[0051] Technical Advantages Explanation Key active ingredients (such as cordycepin and tanshinone) are delivered efficiently using nanotechnology.

[0052] Process integrity: From raw material pretreatment to final product filling, the entire process covers all component processing steps; Define process parameters (such as temperature, pressure, and encapsulation rate) to ensure batch consistency.

[0053] Innovation is reflected in: By integrating water extraction, alcohol extraction, supercritical extraction and nanotechnology, it breaks through the limitations of traditional Chinese medicine preparations; By using glycyrrhizic acid and menthol in synergistic flavor correction, the bitter taste of traditional Chinese medicine atomized liquid can be solved.

[0054] The herbal nebulized inhalation preparation provided by this invention scientifically combines 15 active ingredients from traditional Chinese medicines, including Houttuynia cordata, ginseng, and Eucommia ulmoides, and utilizes fractional extraction and nano-encapsulation technology, resulting in the following significant beneficial effects: Highly effective tobacco alternative: The formulation mimics the taste of traditional cigarettes (92% of users agree), and reduces the urge to smoke by 78% within 24 hours, which is significantly better than commercially available e-cigarettes (45%). Multi-target therapy: Through the synergistic mechanism of "clearing the lungs, tonifying the kidneys, and strengthening the spleen", it simultaneously alleviates withdrawal symptoms (reduced anxiety behavior in rats by 68%), repairs lung damage (IL-6 decreased by 42%), and improves metabolism (blood viscosity decreased by 15%). Technological breakthrough: Nanoliposome technology enables a lung deposition rate of 65% (compared to ≤30% for traditional formulations), an active ingredient release rate of over 90% within 3 hours, and a stability retention rate of ≥95% within 6 months; Safety advantages: It contains no chemically synthesized addictive ingredients, and no adverse reactions such as palpitations or respiratory irritation have been reported in clinical trials, which is in line with the WHO harm reduction strategy.

[0055] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0056] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A nebulized inhalation formulation based on traditional Chinese medicine ingredients, characterized in that, It consists of the following raw materials in parts by weight: Lung-clearing group: 10-15 parts of houttuynia cordata extract, 5-8 parts of mulberry leaf flavonoids, and 4-6 parts of total anthraquinones from cassia seed; Qi-tonifying group: 5-10 parts ginseng extract, 2-5 parts cordycepin; Kidney-tonifying group: 3-8 parts of Cistanche deserticola polysaccharide and 3-5 parts of Eucommia ulmoides total glycosides; Spleen-strengthening and blood-activating group: 5-10 parts of Poria polysaccharide, 2-4 parts of Tanshinone; Calming and tranquilizing group: 1-3 parts agarwood volatile oil, 2-4 parts lily saponins; Atomizing carrier: 30-50 parts vegetable glycerin, 10-20 parts propylene glycol; Flavoring agents: 0.5-1 part menthol, 0.2-0.5 part glycyrrhizic acid.

2. The nebulized inhalation formulation based on traditional Chinese medicine ingredients according to claim 1, characterized in that: The cordycepin and agarwood volatile oil are encapsulated using liposome encapsulation technology, with liposome particle size of 50-100nm and encapsulation rate ≥85%.

3. The nebulized inhalation formulation based on traditional Chinese medicine ingredients according to claim 1, characterized in that: The mulberry leaf flavonoids and poria cocos polysaccharides are encapsulated in chitosan-sodium alginate microspheres with a particle size of 100-200 nm and a sustained release time of ≥6 hours.

4. The nebulized inhalation formulation based on traditional Chinese medicine ingredients according to claim 1, characterized in that: The houttuynia cordata extract was prepared by water extraction and has a total flavonoid content of ≥40%.

5. The nebulized inhalation formulation based on traditional Chinese medicine ingredients according to claim 1, characterized in that: The total glycosides from Eucommia ulmoides were prepared by alcohol extraction, and the glycoside purity was ≥80%.

6. The application of the nebulized inhalation formulation based on traditional Chinese medicine ingredients according to claim 1 in the preparation of alternative tobacco products, characterized in that: The drug is delivered via nebulized inhalation, with a daily dose of 0.5-2 mL, and is used to relieve nicotine withdrawal symptoms, repair alveolar epithelial damage, reduce serum inflammatory factor levels, and improve blood viscosity.

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