Dihydromyricetin inhalation liquid preparation and preparation method thereof

Abstract

The invention relates to a dihydromyricetin inhalation liquid preparation and a preparation method thereof. The dihydromyricetin inhalation liquid preparation comprises dihydromyricetin, a stabilizer, an osmotic pressure regulator, a pH value regulator, a cosolvent and a solvent, the content of the dihydromyricetin is 0.1-2 mg / mL, the content of the stabilizer is 0.4-3 mg / mL, the content of the osmotic pressure regulator is 1-10 mg / mL, and the content of the cosolvent is 20-25% V / V; the pH (Potential of Hydrogen) of the liquid preparation is 3.0 to 6.0; according to the dihydromyricetin inhalation solution preparation provided by the invention, the bioavailability of the medicine is effectively improved, the dihydromyricetin inhalation solution preparation has the characteristics of definite medicine effect, reliable quality, high safety and the like, and the preparation method is few in steps, easy to operate and beneficial to industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a dihydromyricetin inhalation liquid preparation and a preparation method thereof. Background Art

[0002] Dihydromyricetin is a dihydroflavonol compound widely found in plants of the genus Ampelopsis in the grape family. It is also known as dihydromyricetin, ampelopsis, and ampelopsis. Dihydromyricetin is a white needle-shaped crystal with a molecular formula of C 15 H 12 O8 (molecular structure as follows), relative molecular mass is 320.25, chemical structure is (2R, 3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)benzodihydropyran-4-one, melting point is 245-246℃, solubility is low at room temperature and in cold water, it is easily soluble in methanol, ethanol, acetone, and insoluble in chloroform and petroleum ether.

[0003] A large number of modern pharmacological and clinical studies have confirmed that dihydromyricetin has multiple activities such as anti-inflammatory, anti-tumor, antioxidant, hypoglycemic, lipid-regulating, and liver-protecting. In recent years, the antibacterial and antiviral activities of dihydromyricetin have attracted the attention of pharmaceutical workers. Studies on the antibacterial activity of dihydromyricetin have found that dihydromyricetin can inhibit Vibrio parahaemolyticus. In addition, dihydromyricetin has a broad-spectrum antibacterial activity and has good active inhibitory effects on Staphylococcus aureus, Shigella flexneri, Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli, Klebsiella pneumoniae, Salmonella paratyphi B, and Bacillus subtilis. Dihydromyricetin has also been reported in its antiviral effects, but related studies are relatively rare. Ou Xianhong et al. selected dihydromyricetin, the main component of total flavonoids from rattan tea, and used serum pharmacology methods to observe its inhibitory effect on hepatitis B virus in HepG2.2.15 cell culture. They found that dihydromyricetin had a certain inhibitory effect on the secretion of HBsAg and HBeAg by HepG2.2.15 cells, and speculated that its antiviral effect was produced by limiting the replication of hepatitis B virus. Zhou et al. used dihydromyricetin in vitro test to evaluate the inhibitory effect of dihydromyricetin on HSV-1 by detecting the expression of herpes simplex virus type 1 (HSV1) related genes in Vero cells. They found that dihydromyricetin can significantly inhibit the activity of HSV-1 virus. Real-time quantitative PCR and enzyme-linked immunosorbent assay were used to deeply study the molecular mechanism of dihydromyricetin's anti-HSV-1 viral activity. The results showed that dihydromyricetin inhibited the activation of NF-xB by specifically inhibiting the mRNA level of TLR9, causing the degradation of TNF-a and the nuclear translocation of p65, and finally inhibited HSV-1 infection. Liu Miaomiao et al. found through cell experiments that dihydromyricetin showed good antiviral activity at both the molecular biological level and the protein level. Different dosing methods and multiple experiments proved that dihydromyricetin exerted antiviral activity by inhibiting the early replication of the virus. A large number of studies have found that it can combine with the PB2cap structure to have a certain inhibitory effect on the activity of the influenza virus vRNP complex, and there is a concentration correlation. 3-chymotrypsin-like protease (3CLpro) is an important target for the treatment of coronavirus diseases including COVID-19 infection. Preliminary research results show that Ampelopsis grossedentata extract (AGE) has strong SARS-CoV-2-3CLpro inhibitory activity, and the flavonoids in AGE (main component dihydromyricetin) have significant time-dependent inhibitory effects on SARS-CoV-2-3CLpro. CN113350330A discloses the use of myricetin compounds in the preparation of drugs for the prevention and treatment of COVID-19 infection, which gives it certain advantages in the research and development of antiviral drug treatment.

[0004] Although dihydromyricetin has a wide range of pharmacological activities, its solubility is poor, which limits its application. For example, CNCN108670953A and CN115708806A respectively studied and developed nanomicelle preparations and nanosuspensions to solve the technical problem of poor water solubility.

[0005] Inhalation preparations are preparations that allow drugs to reach the lungs through the respiratory tract with the inhaled airflow to exert their therapeutic effects. Due to the special physiological structure of the lungs, inhalation administration has obvious advantages: the alveoli have a large area, rich capillaries, and the epithelial cell layer of the alveoli is very thin, so the drug exchange is fast; the biological metabolic enzyme activity in the lungs is low, which can weaken the hydrolysis of protein and peptide drugs; and it can also avoid the first-pass effect of the liver. These advantages make inhalers the most market-potential pulmonary administration dosage form. At present, inhalation preparations are mainly divided into inhalation powders, inhalation aerosols, liquid preparations for nebulizers, and inhalation sprays. Inhalation solution preparations have low production costs, are convenient for clinical use, are administered by atomization inhalation, have high quality standards, have no gastrointestinal toxicity and irritation, and have the characteristics of fast absorption, high efficacy, and high bioavailability. At present, no dihydromyricetin inhalation solution is available on the market at home and abroad.

[0006] In view of this, there is an urgent need for a dihydromyricetin inhalation liquid preparation to meet the strong demand for clinical medication and fill the gap in domestic dihydromyricetin inhalation solution. Summary of the invention

[0007] The purpose of the present invention is to overcome the defects in the prior art, provide a dihydromyricetin inhalation liquid preparation, and also provide a preparation method thereof.

[0008] To achieve the above object, the technical solution adopted by the present invention is: On one hand, the present invention provides a dihydromyricetin inhalation liquid preparation, which comprises dihydromyricetin, a stabilizer, an osmotic pressure regulator, a pH regulator, a cosolvent and a solvent; the content of the dihydromyricetin is 0.1-2 mg / mL, the content of the stabilizer is 0.4-3 mg / mL, the content of the osmotic pressure regulator is 1-10 mg / mL, and the content of the cosolvent is 20-25% V / V; the pH of the liquid preparation is 3.0-6.0; and the solvent is selected from purified water and water for injection.

[0009] As some preferred embodiments of the present invention, the content of dihydromyricetin is 1-2 mg / mL.

[0010] As some preferred embodiments of the present invention, the stabilizer is selected from ascorbic acid or sodium metabisulfite.

[0011] As some preferred embodiments of the present invention, the stabilizer is sodium metabisulfite, and the content thereof is 2-3 mg / mL.

[0012] As some preferred embodiments of the present invention, the co-solvent is selected from ethanol or propylene glycol.

[0013] As some preferred embodiments of the present invention, the osmotic pressure regulator is selected from one or more of sodium chloride, potassium chloride, magnesium chloride, calcium chloride and glucose.

[0014] As some preferred embodiments of the present invention, the pH adjuster is selected from one or more of disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, hydrochloric acid, sodium hydroxide or sodium bicarbonate.

[0015] As some preferred embodiments of the present invention, the pH adjuster is a phosphate buffer composed of disodium hydrogen phosphate and sodium dihydrogen phosphate and hydrochloric acid.

[0016] As some preferred embodiments of the present invention, the composition comprises dihydromyricetin, sodium pyrosulfite, propylene glycol, sodium chloride and a phosphate buffer having a pH of 6, wherein the dihydromyricetin content is 1-2 mg / mL, the amount of sodium pyrosulfite added is 2-3 mg / mL, the amount of sodium chloride added is 6-6.4 mg / mL, and the volume ratio of propylene glycol to phosphate buffer is 1:3-4.

[0017] Another aspect of the present invention provides a method for preparing the above-mentioned dihydromyricetin inhalation liquid preparation, which specifically comprises the following steps: S1: Add a pH regulator and an osmotic pressure regulator to the solvent to adjust the pH to 3.0-6.0; S2: adding dihydromyricetin and cosolvent in sequence, stirring to dissolve; S3: Add stabilizer and disperse evenly by ultrasonication; S4: Sterilize by filtering through a 0.22 μm filter membrane.

[0018] The beneficial effects of adopting the above technical solution are: 1. The dihydromyricetin inhalation solution preparation provided by the present invention has clear efficacy and reliable quality.

[0019] 2. The dihydromyricetin inhalation solution preparation provided by the present invention does not contain any preservatives, thereby making it safer.

[0020] 3. The dihydromyricetin solution preparation for inhalation provided by the present invention is administered via the lungs, which greatly improves the bioavailability compared with other administration methods, especially increases the lung and blood concentrations at the same time.

[0021] 4. The preparation method of the dihydromyricetin solution preparation for inhalation of the present invention has few steps, is easy to operate, and is conducive to industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the specific implementation of the present invention or the technical solution in the prior art, the drawings required for use in the specific implementation or the description of the prior art are briefly introduced below.

[0023] Figure 1 This is the blood drug concentration-time curve of the metabolism of dihydromyricetin (DMY) in mice in Experimental Example 2 of the present invention; Figure 2 This is a comparison chart of rat lung function test in Experimental Example 3 of the present invention; Figure 3 This is a tissue section of a rat in Test Example 3 of the present invention (H&E×200). DETAILED DESCRIPTION

[0024] In order to make the purpose, technical scheme and advantages of the present invention clearer, the invention is described clearly and completely in conjunction with specific embodiments below, which is only for the convenience of describing the present invention and cannot be understood as limiting the present invention. The test methods and operations in this embodiment are conventional methods and conventional operations unless otherwise specified; the raw materials, reagents, etc. used are commercially available products unless otherwise specified.

[0025] Example 1 Prescription composition: Among them, phosphate buffer (pH 6) was prepared as follows: the concentration of Na2HPO4 was 8 mM, the concentration of NaH2PO4 was 2 mM, and the pH was adjusted to 6 with HCl.

[0026] Preparation method: S1: Prepare the above phosphate buffer, take 1.5 mL and add 12 mg of sodium chloride; S2: Add the prescribed amount of dihydromyricetin and propylene glycol in sequence and stir evenly; S3: adding sodium metabisulfite and dispersing evenly by ultrasonication; S4: sterilize by filtering through a 0.22 μm filter membrane to obtain a dihydromyricetin inhalation solution preparation.

[0027] Example 2 Prescription composition: Among them, phosphate buffer (pH 6) was prepared as follows: the concentration of Na2HPO4 was 8 mM, the concentration of NaH2PO4 was 2 mM, and the pH was adjusted to 6 with HCl.

[0028] Preparation method: S1: Prepare the above phosphate buffer, take 1.6 mL, and add sodium chloride; S2: Add the prescribed amount of dihydromyricetin and propylene glycol in sequence and stir evenly; S3: adding sodium metabisulfite and dispersing evenly by ultrasonication; S4: sterilize by filtering through a 0.22 μm filter membrane to obtain a dihydromyricetin inhalation solution preparation.

[0029] Example 3 Prescription composition: Among them, phosphate buffer (pH 6) was prepared as follows: the concentration of Na2HPO4 was 8 mM, the concentration of NaH2PO4 was 2 mM, and the pH was adjusted to 6 with HCl.

[0030] Preparation method: S1: Prepare the above phosphate buffer, take 1.6 mL, and add sodium chloride; S2: Add the prescribed amount of dihydromyricetin and propylene glycol in sequence and stir evenly; S3: adding sodium metabisulfite and dispersing evenly by ultrasonication; S4: sterilize by filtering through a 0.22 μm filter membrane to obtain a dihydromyricetin inhalation solution preparation.

[0031] Example 4 Prescription composition: Among them, phosphate buffer (pH 6) was prepared as follows: the concentration of Na2HPO4 was 8 mM, the concentration of NaH2PO4 was 2 mM, and the pH was adjusted to 6 with HCl.

[0032] Preparation method: S1: Prepare the above phosphate buffer, take 1.6 mL, and add sodium chloride; S2: Add the prescribed amount of dihydromyricetin and propylene glycol in sequence and stir evenly; S3: adding sodium metabisulfite and dispersing evenly by ultrasonication; S4: sterilize by filtering through a 0.22 μm filter membrane to obtain a dihydromyricetin inhalation solution preparation.

[0033] Example 5 Prescription composition: Among them, phosphate buffer (pH 6) was prepared as follows: the concentration of Na2HPO4 was 8 mM, the concentration of NaH2PO4 was 2 mM, and the pH was adjusted to 6 with HCl.

[0034] Preparation method: S1: Prepare the above phosphate buffer, take 1.6 mL, and add sodium chloride; S2: Add the prescribed amount of dihydromyricetin and propylene glycol in sequence and stir evenly; S3: Add ascorbic acid and disperse evenly by ultrasonication; S4: sterilize by filtering through a 0.22 μm filter membrane to obtain a dihydromyricetin inhalation solution preparation.

[0035] Test Example 1 Physical and Chemical Property Testing The surface tension and viscosity of the preparation prepared in Example 1 were tested. The specific testing methods are as follows: Surface tension test: Use a tensiometer to test the surface tension of the drug solution. Before testing the sample, clean the platinum plate with pure water, then use an alcohol lamp to burn it until the platinum plate is red. After it cools down, hang the platinum plate on the ring stand. Select a suitable test bench height, inject about 50mL of drug solution into the beaker, and automatically test to obtain the tension value. Select at least three batches of samples for repeated testing.

[0036] Viscosity test: Use a viscometer to test the viscosity of the drug solution. Add 300 mL of drug solution into the beaker each time, and then test according to the standardized operating procedure of the viscosity test. Select at least three batches of samples for repeated testing.

[0037] Results: The results of surface tension and viscosity are shown in Table 1.

[0038] Table 1 Physicochemical properties of DMY inhalation solution Experimental Example 2: Pharmacokinetics and tissue distribution of dihydromyricetin inhalation liquid preparation 1. Establishment of in vivo analysis method 1.1 Preparation of standard solution Preparation of standard stock solution: accurately weigh an appropriate amount of DMY, place it in a 25 mL volumetric flask, dissolve it in methanol and dilute to the mark, shake well to obtain a 100 μg / mL DMY reference stock solution. Store in a refrigerator at 4°C for future use.

[0039] Preparation of internal standard solution: Accurately weigh an appropriate amount of dihydroquercetin, place it in a 25 mL volumetric flask, dissolve it with methanol and dilute it to the scale, shake well to obtain a 100 μg / mL dihydroquercetin internal standard solution, and store it in a refrigerator at 4°C for later use.

[0040] 1.2 Pretreatment of plasma and tissue samples Tissue sample pretreatment: take 100 mg of blank tissue, add 200 μL methanol (1% phosphoric acid), homogenize the tissue, and then centrifuge at 12000 r / min for 20 min, take the supernatant, about 100 μL, add 100 μL methanol (1% phosphoric acid), 10 μL internal standard (100 μg / mL), vortex for 30 seconds, and then centrifuge at 12000 r / min for 20 min, take 20 μL of supernatant, and inject for detection.

[0041] Pretreatment of plasma samples: take blank plasma and centrifuge it at 4000r / min for 10min, take 150μL of supernatant, add 150μL of methanol (1% phosphoric acid), 10μL of internal standard (100μg / mL), vortex for 30 seconds, then centrifuge it at 12000r / min for 20min, take 20μL of supernatant, and inject it for detection.

[0042] 1.3 Chromatographic detection conditions Column: kromasil TM C18 (4.6×250 mm, 5μm); Mobile phase: methanol-0.1% phosphoric acid aqueous solution (35:65, V:V); Flow rate: 1.0 mL / min; Detection wavelength: 291nm; Column temperature: 30°C; Injection volume: 20 μL.

[0043] Internal standard: dihydroquercetin.

[0044] 2. Pharmacokinetics and tissue distribution of dihydromyricetin inhalation liquid preparation 2.1 Dosage regimen Atomization inhalation group: The inhalation liquid preparation prepared in Example 1 was used, according to the formula: D=C×V×DI×T. D is the total dose of atomization administration, C is the saturation density of the drug gas in the closed container (the instant saturated gas drug in the closed container is liquefied and collected, and quantitatively analyzed and converted by high performance liquid chromatography), V is the respiratory volume per minute of the experimental animal (about 1.0 L / min / kg for mice), DI is the distribution coefficient of respiratory gas in the animal's lungs (about 0.3 for mice), and T is the atomization time. According to the formula calculation, the atomization administration dose is about 13.2 mg / kg.

[0045] Intragastric gavage group: an appropriate amount of dihydromyricetin (DMY) was mixed with 0.5% sodium carboxymethylcellulose solution to prepare a 20 mg / mL suspension, which was then administered by intragastric gavage at a dose of 200 mg / kg.

[0046] 2.2 Test methods 72 adult KM female mice were randomly divided into an oral gavage group and an aerosol inhalation group, 36 mice in each group, 9 time points, 4 mice at each time point, fasting for 12 hours, free access to water. According to relevant literature, the sampling time points for the pharmacokinetics and tissue distribution test of DMY in mice were determined. Blood was collected from the canthus vein of mice at 5, 10, 20, 30, 45, 60, 90, 120 and 150 minutes after administration, placed in sodium heparin tubes and numbered, and immediately centrifuged at 4000r / min for 10 minutes at 4°C, and the supernatant was placed in a refrigerator at -20°C for use. Lung, heart, liver, and kidney tissues were also taken, and the surface blood and contents were rinsed with cold saline, and the water was absorbed by filter paper, stored at -80°C for use. The plasma and tissue samples collected at different time points were tested using the aforementioned HPLC detection method, and the peak area of ​​the chromatogram was recorded and brought into the standard curve to calculate the DMY in vivo drug concentration at different time points.

[0047] 2.3 Calculation of pharmacokinetic parameters The pharmacokinetic parameters of DMY in vivo were calculated and analyzed using the non-compartmental model using DAS 3.2.2 pharmacokinetic software, including the maximum plasma concentration (C max ), reach C max Time (T max ), area under the drug-time curve (AUC), mean residence time (MRT) and half-life (T 1 / 2 ).

[0048] 2.4 Results 2.4.1 Blood drug concentration-time curve After aerosol administration and oral administration of DMY inhalation preparation, the DMY concentration in mouse plasma and various tissues was measured at different time points. The DMY blood concentration-time curve is shown in Figure 1 shown.

[0049] 2.4.2 Pharmacokinetic parameters Table 2 Main pharmacokinetic parameters of DMY metabolism in mice (n=4) Compared with oral administration, after aerosolized DMY, the T 1 / 2 and MRT 0-∞ The time was prolonged, indicating that the elimination of DMY in the DMY inhalation preparation in mice was slowed down and the residence time was prolonged; the nebulized dose was 13.2 mg / kg, and the oral dose was 200 mg / kg. The relative bioavailability F = AUC 0-∞ / D (dose of medication) 雾化 / AUC 0-∞ / D (dose of medication) 灌胃×100%=3123.25%, indicating that DMY inhalation preparations can significantly increase drug exposure in mice and improve bioavailability. DMY reached its peak in liver, heart, lung, and kidney 30 minutes after administration, and the DMY drug content in each tissue was close to 10% of the maximum concentration at 150 minutes, indicating that DMY was eliminated quickly in mice and was not easy to accumulate.

[0050] It can be seen that the residence time and half-life of the drug in the body are relatively prolonged after aerosol administration, and the drug concentration in the mouse lungs is higher than that in other organs and tissues. Aerosol inhalation has obvious lung targeting and relatively reduces the distribution of DMY in other tissues. The aerosol administration of the present invention also increases the concentration in the blood, and at the same time solves the problem of low bioavailability of oral preparations, which can provide a reference for the clinical application of DMY inhalation preparations.

[0051] Test Example 3 Safety Evaluation 1. Experimental Animals Healthy female SD rats weighing 200-250 g were housed in clean cages with free access to food and water. The temperature was controlled at (25±2)℃, the humidity was 50-75%, and the light cycle was 12 h.

[0052] 2. Methods 2.1 Experimental Grouping Six healthy female SD rats were randomly selected and divided into two groups, namely a preparation group (Example 1) and a physiological saline group.

[0053] 2.2 Administration The rats were induced to enter the semi-enclosed device, and the air inlet of the device was connected to the outlet of the nebulizer to ensure that the nebulized gas effectively entered the device. 2 mL of the DMY inhalation solution (2 mg / mL) prepared in Example 1 or normal saline was added to the nebulizer cup, and the nebulizer was turned on for nebulization administration. The experiment was carried out for 7 consecutive days, with administration once a day. At the administration time point on the 7th day, the lung function of the rats was tested. After the measurement, the heart, liver, lungs and kidneys were dissected and separated, and the sections were stained and observed.

[0054] 2.3 Pulmonary function test in rats The lung function is measured by a small animal whole body volume scanning system. During the operation, the airflow changes are detected by sensors to obtain respiratory parameters and pressure signals, thereby obtaining a series of parameters of the animal's lung function.

[0055] 2.4 Histopathological analysis The dissected heart, liver, lung, and kidney tissues were immediately rinsed of blood stains with physiological saline, dried with filter paper, and fixed in 4% formaldehyde solution. After fixation, they were dehydrated and embedded. Finally, the sections were sliced ​​and stained with H&E and observed under a microscope to check whether there were pathological phenomena such as alveolar swelling, congestion, infiltration and hyperplasia in the lung tissue, so as to examine the irritation of DMY inhalation preparations to the lung tissue.

[0056] 3. Results 3.1 Pulmonary function test in rats There were no significant differences between the saline group and the preparation group in respiratory rate, tidal volume, minute ventilation, inspiratory time, expiratory time, airway narrowing index, apnea, and maximum inspiratory flow rate. In general, the DMY preparation has good safety and less damage to the lungs. For details, see Figure 2 .

[0057] 3.2 Histopathological analysis like Figure 3 As shown, the tissue section staining results showed that there was no obvious effect on the tissues in the normal saline group and the DMY inhalation preparation group after short-term nebulized administration, and there was no significant difference between the two groups.

[0058] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A dihydromyricetin inhalation liquid preparation, characterized in that: The invention comprises dihydromyricetin, a stabilizer, an osmotic pressure regulator, a pH regulator, a solubilizing agent and a solvent; the content of the dihydromyricetin is 0.1-2 mg / mL, the content of the stabilizer is 0.4-3 mg / mL, the content of the osmotic pressure regulator is 1-10 mg / mL, and the content of the solubilizing agent is 20-25% V / V; the pH of the liquid preparation is 3.0-6.0; and the solvent is selected from purified water and water for injection.

2. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The content of the dihydromyricetin is 1-2 mg / mL.

3. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The stabilizer is selected from ascorbic acid or sodium metabisulfite.

4. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The stabilizer is sodium pyrosulfite, and the content is 2-3 mg / mL.

5. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The co-solvent is selected from ethanol or propylene glycol.

6. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The osmotic pressure regulator is selected from one or more of sodium chloride, potassium chloride, magnesium chloride, calcium chloride and glucose.

7. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The pH adjuster is selected from one or more of disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, hydrochloric acid, sodium hydroxide or sodium bicarbonate.

8. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The pH value regulator is a phosphate buffer composed of disodium hydrogen phosphate and sodium dihydrogen phosphate and hydrochloric acid.

9. The dihydromyricetin inhalation liquid preparation according to claim 1, characterized in that The invention comprises dihydromyricetin, sodium pyrosulfite, propylene glycol, sodium chloride and a phosphate buffer solution with a pH of 6, wherein the content of dihydromyricetin is 1-2 mg / mL, the amount of sodium pyrosulfite added is 2-3 mg / mL, the amount of sodium chloride added is 6-6.4 mg / mL, and the volume ratio of propylene glycol to phosphate buffer solution is 1:3-4.

10. A method for preparing a dihydromyricetin inhalation liquid preparation according to any one of claims 1 to 9, characterized in that: The specific steps include: S1: Add a pH regulator and an osmotic pressure regulator to the solvent to adjust the pH to 3.0-6.0; S2: adding dihydromyricetin and cosolvent in sequence, stirring to dissolve; S3: Add stabilizer and disperse evenly by ultrasonication; S4: Sterilize by filtering through a 0.22 μm filter membrane.

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