Method for treating chronic bronchitis by using Tibetan medicine Bangjin Alba powder based on aerosol inhalation

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations and atomization medicine delivery, in particular to a method for treating chronic bronchitis based on Tibetan medicine Bunjinjian San, which comprises the following steps: S1, drying Bunjinjian San raw medicine at low temperature, and carrying out superfine grinding to obtain raw medicine micro powder; s2, removing resin and grease impurities; s3, carrying out vacuum concentration on the obtained filtrate; s4, treating the concentrated extract through an ultrafiltration membrane; s5, preparing the clarified extracting solution into atomized liquid; s6, medicine aerosol is formed through ultrasonic oscillation; s7, guiding the chronic bronchitis patient to inhale the drug aerosol; s8, after all the inhalation treatment courses are completed, a treatment conclusion report is obtained. According to the present invention, the particle size controllable Bunjinjian aerosol is prepared through the continuous purification-clarification-sterilization-atomization process, such that the targeted lower respiratory tract drug delivery is achieved, the preparation quality and the equipment smoothness are ensured, the local treatment effect is improved, and the whole body side effect is reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations and aerosol drug delivery, and in particular to a method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on aerosol inhalation. Background Art

[0002] Chronic bronchitis is a common respiratory disease characterized by persistent airway inflammation and mucus hypersecretion. Long-term recurrent coughing and sputum production seriously reduce the quality of life of patients. Currently, oral expectorants, bronchodilators and systemic glucocorticoids are mainly used in clinical treatment, but the oral route has limitations such as a large first-pass effect, strong gastrointestinal irritation, and low drug concentration entering the lungs. Although injectable preparations have a rapid onset of action, they are prone to induce systemic adverse reactions and poor compliance with long-term maintenance treatment. The Tibetan medicine Bangjin Jiao'a San, derived from the "Four Medical Classics", has the effects of clearing heat and benefiting the lungs, relieving cough and reducing phlegm, and relieving asthma. It has always been used in the clinical folk medicine of chronic bronchitis. However, this prescription mainly uses traditional powder for oral administration. The powder is easy to choke when taken, and the active ingredients have difficulty in fully reaching the lower respiratory tract, resulting in fluctuations in efficacy. Modern nebulization inhalation technology can directly atomize the drug solution into an aerosol with a particle size of 2-5μm and deposit it in the small bronchi and alveolar areas. It is recognized as an ideal drug delivery method to improve local efficacy and reduce systemic side effects.

[0003] Existing technologies fail to address key bottlenecks in the nebulized inhalation process of Bangjin Jiao'a Powder: First, the raw medicinal material contains high levels of resin and oil impurities, which easily accumulate in the nebulizer pipeline and cause blockage. Second, the liquid obtained by conventional water decoction or simple water-alcohol extraction has high viscosity and many particulate impurities, making it difficult to pass through a 0.22μm sterile filter membrane to achieve terminal sterilization. Third, there is a lack of standardized particle size closed-loop control, and the wide distribution of atomized particle size leads to uncontrollable deposition sites. Fourth, the composition of different batches of medicinal materials varies significantly, and the lack of a systematic process chain from powder pretreatment to extraction and purification, aerosol preparation, and use evaluation makes it difficult to ensure stable efficacy. Therefore, there is an urgent need to provide a method for treating chronic bronchitis with the Tibetan medicine Bangjin Jiao'a Powder through nebulized inhalation to address the above issues. Summary of the Invention

[0004] Based on the above objectives, the present invention provides a method for treating chronic bronchitis based on aerosol inhalation of the Tibetan medicine Bangjinjiaoa San.

[0005] The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation comprises the following steps:

[0006] S1: The Bangjin Jiao A San technical drug is dried at low temperature and then ultrafine ground to obtain technical drug powder;

[0007] S2: The technical powder obtained in S1 is placed in a supercritical CO2 extraction device to remove resin and oil impurities to obtain purified powder;

[0008] S3: Using the purified powder as the only raw material, a water-ethanol gradient extraction is performed and the obtained filtrate is concentrated under reduced pressure to obtain a concentrated extract;

[0009] S4: processing the concentrated extract through an ultrafiltration membrane to remove high molecular weight impurities and obtain a clarified extract;

[0010] S5: Using normal saline as solvent, prepare the clarified extract into a nebulized solution and perform sterile filtration;

[0011] S6: The atomized liquid is loaded into a medical ultrasonic atomization device to form a drug aerosol through ultrasonic oscillation;

[0012] S7: Instruct patients with chronic bronchitis to use a nebulizer inhalation device to inhale the drug aerosol;

[0013] S8: After completing the entire inhalation treatment course, the inhalation process data is counted and processed to produce a treatment conclusion report.

[0014] Optionally, the S1 specifically includes:

[0015] S11: The raw Bangjin Jiaoasan herbs were manually cleaned to remove sand, branches, and impurities, and then cut into small pieces with a length of 3–5 cm.

[0016] S12: Place the small segments cut in S11 in a hot air circulation drying oven, control the temperature at 40–60°C, relative humidity ≤30%, and wind speed at 0.3–0.6 m / s, and dry for 4–8 hours to obtain a preliminary dried material;

[0017] S13: The preliminary dried material is loaded into an airflow ultrafine pulverizer, pulverized using a working air pressure of 0.8–1.2 MPa, and separated through a 600-mesh sieve to collect medicinal material micropowder with a particle size D90 controlled at 10–25 μm.

[0018] Optionally, the S2 specifically includes:

[0019] S21: The medicinal material powder obtained in S1 is placed into an extraction tank of a supercritical CO2 extraction device, and CO2 is pre-pressed to 8MPa–12MPa at room temperature;

[0020] S22: Under the conditions of temperature 40℃–60℃ and pressure 25MPa–30MPa, supercritical CO2 was introduced with a CO2 flow rate of 1.0L / min–2.0L / min for continuous extraction for 30min–45min;

[0021] S23: After the extraction is completed, the pressure is reduced to normal pressure at a rate of 5 MPa / min–10 MPa / min, and the discharge valve is opened to remove the residue;

[0022] S24: The obtained residue is placed in a vacuum drying oven at 50° C.–60° C. and a vacuum degree of 0.08 MPa–0.12 MPa and dried for 2 h–4 h to obtain a purified powder.

[0023] Optionally, the S3 specifically includes:

[0024] S31: Add the purified powder obtained in S2 and deionized water in a material-liquid mass ratio of 1:8 to 1:12 into a sealed extraction tank, reflux and extract at 60°C–80°C for 60–90 minutes, and take the first extract;

[0025] S32: Filter the first extract and collect the residue, then reflux extract the residue with a 30% ethanol solution at a feed-liquid mass ratio of 1:10 to 1:15 for 40 min–60 min to obtain a second extract at the same temperature range;

[0026] S33: reflux extraction of the filter residue after the second extraction with a 70% ethanol solution at a feed-liquid mass ratio of 1:8 to 1:12 for 30 min–45 min to obtain a third extract;

[0027] S34: The extracts from the first, second, and third sections are combined, and after removing suspended solids through a plate and frame filter, they are concentrated under reduced pressure at 50°C–60°C and a vacuum degree of 0.08 MPa–0.09 MPa until the relative density of the extract reaches 1.10–1.25 to obtain a concentrated extract.

[0028] Optionally, the S4 specifically includes:

[0029] S41: The concentrated extract obtained in S3 is added to sterile purified water in a volume ratio of 1:1 to 1:3, and the viscosity of the solution is adjusted to 30-50 mPa·s to obtain a pretreated solution;

[0030] S42: The pretreated liquid is transported to a hollow fiber ultrafiltration membrane module equipped with a molecular weight cutoff of 8 kDa–12 kDa, and ultrafiltration is performed at a temperature of 25°C–35°C, a transmembrane pressure of 0.15 MPa–0.30 MPa, and a circulation flow rate of 0.5 m / s–1.0 m / s. The operation is continued until the volume of the retentate is 20%–30% of the initial volume;

[0031] S43: Sterile purified water is continuously added to the ultrafiltration system for tangential flow displacement. The displacement water volume is 2–3 times the initial feed volume. The same operating conditions as S42 are maintained and the permeate is collected.

[0032] S44: The permeates obtained in S42 and S43 are combined and concentrated under vacuum conditions of 0.06 MPa-0.08 MPa and a temperature of 45° C.-55° C. to a solid content of 8%-12% to obtain the clarified extract.

[0033] Optionally, the S5 specifically includes:

[0034] S51: introducing the clarified extract obtained in S4 into 0.9% sodium chloride injection at a volume ratio of 1:4 to 1:8, and mixing while stirring until the conductivity of the solution stabilizes;

[0035] S52: Measure the pH of the resulting mixture using a pH meter and adjust the pH to 6.5–7.4 by microtitration using injection-grade sodium bicarbonate solution;

[0036] S53: Pre-filter the pH-adjusted mixed solution through a 0.45 μm pre-filter membrane to remove visible particles and suspended matter;

[0037] S54: The pre-filtered solution is continuously filtered through a 0.22 μm pore size hydrophilic polyethersulfone sterile filter membrane at a temperature of 15°C–25°C and a pressure of 0.08 MPa–0.12 MPa for terminal filtration, and the filtrate is collected as the atomized liquid;

[0038] S55: The obtained atomized liquid is aseptically filled and sealed for later use.

[0039] Optionally, the S6 specifically includes:

[0040] S61: Sample the atomized liquid obtained in S5 at a volume of 2 mL–5 mL per treatment and inject it into the liquid storage tank of the medical ultrasonic atomizer, and then tightly close the storage tank cap;

[0041] S62: Set the ultrasonic transducer operating frequency to 1.6MHz–2.2MHz and the transducer surface power density to 0.5W / cm 2 –1.5W / cm 2 , starting the device to generate an initial atomized aerosol;

[0042] S63: Input medical air at a flow rate of 4 L / min–8 L / min into the atomizing chamber of the atomizing device, and output the aerosol to the inhalation port;

[0043] S64: Real-time measurement of the aerosol mass median particle size. When the measured value exceeds the range of 2μm–5μm, adjust the ultrasonic power or airflow rate until the particle size falls back into the range.

[0044] Optionally, the S7 specifically includes:

[0045] S71: Connect the drug aerosol delivery tube output by S6 to the disposable oral and nasal mask and set the air supply flow rate to 4L / min–6L / min;

[0046] S72: Have the chronic bronchitis patient sit in a 70°–90° position, put on the mask, ensure that the edge of the mask completely fits the face, and start the nebulizer inhalation device;

[0047] S73: Instruct the patient to cycle through the mouth for 3–5 seconds of constant inhalation, breath holding for 1–2 seconds, and nasal exhalation for 4–6 seconds until all the nebulized liquid is atomized.

[0048] S74: When the remaining liquid volume in the nebulizer drops to 0.3 mL and the nebulization rate is lower than 0.1 mL / min, stop the gas supply and remove the mask;

[0049] S75: After inhalation, instruct the patient to rinse the mouth with 10 mL–20 mL of sterile water and wipe the inner wall of the mask dry, then run the device idling for 30 s–60 s to expel residual aerosol.

[0050] Optionally, the S8 specifically includes:

[0051] S81: After the patient completes three consecutive complete courses of nebulized inhalation therapy, each course includes two inhalations per day, each inhalation of nebulized liquid is approximately equal to 3g of the original medicinal material, for 5 days, and the total treatment period is 15 days;

[0052] S82: Collect the patient's nebulization inhalation records during each treatment course, including the duration of each inhalation, the amount of nebulized liquid used, the respiratory rate, and the inhalation-exhalation ratio, and form a treatment course inhalation database;

[0053] S83: Within 72 hours after the third course of treatment, the cough symptom score, sputum volume score, and serum C-reactive protein concentration of the patients were evaluated, and the pre-treatment and post-treatment values ​​of the three indicators were recorded;

[0054] S84: Calculate the improvement rate of each indicator using a standardized algorithm, compare the improvement rate result with a preset statistical template, and confirm whether it meets the set change range;

[0055] S85: Based on the data obtained from S82 and S84, a structured treatment conclusion report is generated, which includes the changing trends of various indicators, the statistics of compliance during the inhalation process, and the final grading evaluation results of the treatment effect.

[0056] Optionally, the S84 specifically includes:

[0057] S841: Import the pre-treatment value and post-treatment value of each indicator obtained in S83 into the data processing module to unify the numerical precision and measurement unit;

[0058] S842: Calculate the improvement rate R for the i-th indicator according to the following formula i , the formula is: Where Vpre,i is the value before treatment, V post,i The calculated value is the post-treatment value, and the calculation result is rounded to one decimal place;

[0059] S843: The improvement rate R of each indicator i The corresponding indicator target interval [α i , β i ] to compare; if R i <α i , then the record evaluation level is not up to standard; if α i ≤R i ≤β i , record as meeting the standard; if R i >β i , recorded as significantly achieved, where α i and β i are the lowest and highest points of the target range respectively.

[0060] Beneficial effects of the present invention:

[0061] The present invention, through the continuous process chain of "low-temperature drying-ultrafine grinding-supercritical CO2 degreasing-gradient extraction-ultrafiltration clarification-isotonic sterile preparation-ultrasonic atomization", systematically solves key process pain points such as resin and grease blockage, high viscosity, large impurity particle size and difficulty in sterile filtration; the prepared atomized liquid has low viscosity and high clarity, can stably pass through a 0.22μm terminal filter membrane to achieve aseptic filling, and outputs drug aerosol with concentrated particle size (2-5μm) under laser diffraction closed-loop control, ensuring smooth equipment operation, controllable particle size and batch-to-batch quality consistency, laying a solid foundation for industrial scale-up.

[0062] The present invention, through the above-prepared Bangjin Jiao A San aerosol can be directly deposited in the small bronchi and alveoli, realizing local high-concentration drug delivery, significantly reducing systemic exposure while maintaining the synergistic effect of traditional Tibetan medicine compound; patients only need to perform home-level nebulization according to the course of treatment to complete the treatment, avoiding oral gastrointestinal irritation and injection adverse reactions, improving compliance and safety margin, and is particularly suitable for the long-term management of chronic bronchitis in the elderly and children in plateau areas. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0064] Figure 1 Schematic diagram of a method for treating chronic bronchitis with Bangjin Jiao A San according to an embodiment of the present invention;

[0065] Figure 2 Schematic diagram of a method for obtaining a clarified extract according to an embodiment of the present invention. DETAILED DESCRIPTION

[0066] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments. It is also noted that, to provide a more detailed description, the following embodiments are best and preferred embodiments, and those skilled in the art may employ alternative methods for implementing certain known technologies. Furthermore, the accompanying drawings are intended only to provide a more detailed description of the embodiments and are not intended to limit the present invention.

[0067] It should be noted that references in the specification to "one embodiment," "an embodiment," "an exemplary embodiment," "some embodiments," etc. indicate that the described embodiments may include specific features, structures, or characteristics, but not every embodiment necessarily includes such specific features, structures, or characteristics. In addition, when specific features, structures, or characteristics are described in conjunction with an embodiment, it is within the knowledge of persons skilled in the relevant art to implement such features, structures, or characteristics in conjunction with other embodiments (whether or not explicitly described).

[0068] In general, terms can be understood, at least in part, from their use in context. For example, depending at least in part on the context, the term "one or more" as used herein can be used to describe any feature, structure, or characteristic in the singular sense, or can be used to describe a combination of features, structures, or characteristics in the plural sense. Additionally, the term "based on" can be understood as not necessarily intended to convey an exclusive set of factors, but can instead, depending at least in part on the context, allow for the presence of other factors that are not necessarily explicitly described.

[0069] Example 1

[0070] like Figure 1-Figure 2 As shown, the method for treating chronic bronchitis based on atomization inhalation of Tibetan medicine Bangjin Jiao A San comprises the following steps:

[0071] S1: The Bangjin Jiao A San technical drug is dried at low temperature and then ultrafine ground to obtain technical drug powder;

[0072] S2: The technical powder obtained in S1 is placed in a supercritical CO2 extraction device to remove resin and oil impurities to obtain purified powder;

[0073] S3: Using the purified powder as the only raw material, a water-ethanol gradient extraction is performed and the obtained filtrate is concentrated under reduced pressure to obtain a concentrated extract;

[0074] S4: processing the concentrated extract through an ultrafiltration membrane to remove high molecular weight impurities and obtain a clarified extract;

[0075] S5: Using normal saline as solvent, prepare the clarified extract into a nebulized solution and perform sterile filtration;

[0076] S6: The atomized liquid is loaded into a medical ultrasonic atomization device to form a drug aerosol through ultrasonic oscillation;

[0077] S7: Instruct patients with chronic bronchitis to use a nebulizer inhalation device to inhale medication aerosols;

[0078] S8: After completing the entire inhalation treatment course, the inhalation process data is counted and processed to produce a treatment conclusion report.

[0079] S1 specifically includes:

[0080] S11: The raw medicinal material of Bangjin Jiao Asan is manually cleaned to remove mud, sand, branches and leaves, and then cut into small pieces with a length of 4 cm;

[0081] S12: Place the small segments cut in S11 in a hot air circulation drying oven, control the temperature at 50°C, relative humidity at 25%, and wind speed at 0.5 m / s, and dry for 6 hours to obtain a preliminary dried material;

[0082] S13: The preliminarily dried material is loaded into an airflow ultrafine pulverizer, pulverized using a working air pressure of 0.9 MPa, and separated through a 600-mesh sieve to collect medicinal material micropowder with a particle size D90 controlled at 15 μm.

[0083] S2 specifically includes:

[0084] S21: The medicinal material powder obtained in S1 is placed into an extraction tank of a supercritical CO2 extraction device, and CO2 is pre-pressed to 10 MPa at room temperature;

[0085] S22: Under the conditions of temperature 50°C and pressure 27 MPa, supercritical CO2 was introduced with a CO2 flow rate of 1.5 L / min and the extraction was continued for 40 min;

[0086] S23: After the extraction is completed, the pressure is reduced to normal pressure at a rate of 8 MPa / min, and the discharge valve is opened to remove the residue;

[0087] S24: The obtained residue was placed in a vacuum drying oven at 55° C. and a vacuum degree of 0.10 MPa and dried for 3 h to obtain purified powder.

[0088] S3 specifically includes:

[0089] S31: Add the purified powder obtained in S2 and deionized water in a material-liquid mass ratio of 1:10 into a sealed extraction tank, reflux and extract at 70°C for 70 minutes, and take the first extract;

[0090] S32: Filter the first extract and collect the residue, then reflux extract the residue with a 30% (v / v) ethanol solution at a feed-liquid mass ratio of 1:13 for 50 minutes to obtain a second extract within the same temperature range;

[0091] S33: The filter residue after the second extraction is further refluxed with a 70% (v / v) ethanol solution at a feed-liquid mass ratio of 1:10 for 40 minutes to obtain a third extract;

[0092] S34: The extracts from the first, second and third sections are combined, and after removing suspended solids through a plate and frame filter, they are concentrated under reduced pressure at 55° C. and a vacuum degree of 0.085 MPa until the relative density (20° C.) of the extract reaches 1.15 to obtain a concentrated extract.

[0093] S4 specifically includes:

[0094] S41: The concentrated extract obtained in S3 is added to sterile purified water at a volume ratio of 1:2, and the viscosity of the solution is adjusted to 40 mPa·s to obtain a pretreated solution;

[0095] S42: The pretreated liquid is transferred to a hollow fiber ultrafiltration membrane module equipped with a molecular weight cutoff of 10 kDa, and ultrafiltration is performed at a temperature of 30°C, a transmembrane pressure of 0.25 MPa, and a circulation flow rate of 0.8 m / s. The operation is continued until the volume of the retentate is 25% of the initial volume;

[0096] S43: Sterile purified water was continuously added to the ultrafiltration system for tangential flow displacement. The displacement water volume was 2.5 times the initial feed volume. The same operating conditions as S42 were maintained and the permeate was collected.

[0097] S44: The permeates obtained in S42 and S43 were combined and concentrated under vacuum of 0.07 MPa and a temperature of 50° C. to a solid content of 10% to obtain a clarified extract.

[0098] S5 specifically includes:

[0099] S51: The clarified extract obtained in S4 is introduced into 0.9% sodium chloride injection at a volume ratio of 1:6, and mixed while stirring until the conductivity of the solution stabilizes;

[0100] S52: measuring the pH of the resulting mixed solution using a pH meter, and adjusting the pH to 7.0 by microtitration using an injection-grade sodium bicarbonate solution;

[0101] S53: Pre-filter the pH-adjusted mixed solution through a 0.45 μm pre-filter membrane to remove visible particles and suspended matter;

[0102] S54: The pre-filtered solution is continuously filtered through a 0.22 μm hydrophilic polyethersulfone sterile filter membrane at a temperature of 20° C. and a pressure of 0.10 MPa for terminal filtration, and the filtrate is collected as the atomized liquid;

[0103] S55: The obtained atomized liquid is aseptically filled and sealed for later use.

[0104] S6 specifically includes:

[0105] S61: sampling the atomized liquid obtained in S5 at a volume of 3 mL per treatment and injecting it into the liquid storage tank of the medical ultrasonic atomization device, and tightly closing the storage tank cap;

[0106] S62: Set the ultrasonic transducer operating frequency to 2.0 MHz and the transducer surface power density to 1.0 W / cm 2 , starting the device to generate an initial atomized aerosol;

[0107] S63: Input medical air at a flow rate of 6 L / min into the atomizing chamber of the atomizing device, and output the aerosol to the inhalation port;

[0108] S64: Measure the aerosol mass median particle size in real time. When the measured value exceeds a predetermined range, adjust the ultrasonic power or airflow rate until the particle size falls back into the range.

[0109] S7 specifically includes:

[0110] S71: Connect the drug aerosol delivery tube output by S6 to the disposable oral and nasal mask and set the air supply flow rate to 5 L / min;

[0111] S72: Have the patient with chronic bronchitis sit in an 80-degree position, put on a mask with the edge of the mask completely fitting the face, and start the nebulizer inhalation device;

[0112] S73: Instruct the patient to follow a 4-second steady-state inhalation through the mouth, 1.5-second breath-hold, and 5-second nasal exhalation cycle until all the nebulized liquid is atomized.

[0113] S74: When the remaining liquid volume in the nebulizer drops to 0.3 mL and the nebulization rate is lower than 0.1 mL / min, stop the gas supply and remove the mask;

[0114] S75: After inhalation, instruct the patient to rinse the mouth with 15 mL of sterile water and wipe the inner wall of the mask dry, then run the device idling for 45 seconds to expel residual aerosol.

[0115] S8 specifically includes:

[0116] S81: After the patient completes three consecutive complete courses of nebulized inhalation therapy, each course includes two inhalations per day, each inhalation of nebulized liquid is approximately equal to 3g of the original medicinal material, for 5 days, and the total treatment period is 15 days;

[0117] S82: Collect the patient's nebulization inhalation records during each treatment course, including the duration of each inhalation, the amount of nebulized liquid used, the respiratory rate, and the inhalation-exhalation ratio, and form a treatment course inhalation database;

[0118] S83: Within 72 hours after the third course of treatment, the cough symptom score, sputum volume score, and serum C-reactive protein concentration of the patients were evaluated, and the pre-treatment and post-treatment values ​​of the three indicators were recorded;

[0119] S84: Calculate the improvement rate of each indicator using a standardized algorithm, compare the improvement rate result with a preset statistical template, and confirm whether it meets the set change range;

[0120] S85: Based on the data obtained from S82 and S84, a structured treatment conclusion report is generated, which includes the changing trends of various indicators, the statistics of compliance during the inhalation process, and the final grading evaluation results of the treatment effect.

[0121] S84 specifically includes:

[0122] S841: Import the pre-treatment value and post-treatment value of each indicator obtained in S83 into the data processing module to unify the numerical precision and measurement unit;

[0123] S842: Calculate the improvement rate R for the i-th indicator according to the following formula i , the formula is: Where V pre,i is the value before treatment, V post,i The calculated value is the post-treatment value, and the calculation result is rounded to one decimal place;

[0124] S843: The improvement rate R of each indicator i The corresponding indicator target interval [α i , β i ] to compare; if R i <α i , then the record evaluation level is not up to standard; if α i ≤R i ≤β i , record as meeting the standard; if R i >β i , recorded as significantly achieved, where α i and β i are the lowest and highest points of the target range respectively.

[0125] Table 1 Preset statistical template comparison example

[0126]

[0127] Example 2

[0128] S1: The raw medicinal material of Bangjin Jiao A San was manually cleaned to remove impurities such as sand, branches and leaves, and then cut into small pieces of 3 cm in length. The cut medicinal material was placed in a hot air circulation drying oven with a set temperature of 40°C, a relative humidity of 28%, and a wind speed of 0.3 m / s for 4 hours to obtain a preliminary dried material. The dried material was then sent to an air flow ultrafine pulverizer and pulverized at an operating pressure of 0.8 MPa. The powder was then graded through a 600-mesh sieve and the medicinal material powder with a particle size D90 of 10 μm was collected for subsequent extraction operations.

[0129] S2: The medicinal material powder obtained in S1 is placed in the extraction tank of a supercritical CO2 extraction device, and CO2 is pre-pressed to 8 MPa at room temperature; then the extraction temperature is set to 40°C and the extraction pressure is set to 25 MPa, and supercritical CO2 is continuously introduced at a CO2 flow rate of 1.0 L / min, and the extraction is continued for 30 minutes to remove resin and oil impurities; after the extraction is completed, the pressure is reduced to normal pressure at a decompression rate of 5 MPa / min, the discharge valve is opened to remove the residue, and the residue is placed in a vacuum drying oven with a vacuum degree of 0.08 MPa and a temperature of 50°C for 2 hours to obtain purified powder;

[0130] S3: The purified powder obtained in S2 was mixed with deionized water at a material-liquid mass ratio of 1:8, and placed in a sealed extraction tank. The mixture was refluxed and extracted at a temperature of 60°C for 60 minutes to obtain a first extract. The filter residue was refluxed and extracted again with a 30% ethanol solution at a material-liquid ratio of 1:10 for 40 minutes to obtain a second extract. The remaining filter residue was refluxed and extracted with a 70% ethanol solution at a material-liquid ratio of 1:8 for another 30 minutes to obtain a third extract. The three extracts were combined, filtered through a plate and frame to remove suspended matter, and then concentrated under reduced pressure at 50°C and a vacuum degree of 0.08 MPa until the relative density of the extract reached 1.10 to obtain a concentrated extract.

[0131] S4: The concentrated extract obtained in S3 was mixed with sterile purified water in a volume ratio of 1:1, and the viscosity of the solution was adjusted to 30 mPa·s to prepare a pretreated feed solution; the feed solution was transferred to a hollow fiber ultrafiltration membrane module with a molecular weight cutoff of 8 kDa. The operating temperature was set at 25°C, the transmembrane pressure was set at 0.15 MPa, and the circulation flow rate was set at 0.5 m / s. Ultrafiltration was continued until the volume of the retentate decreased to 20% of the initial volume; sterile purified water was then added for tangential flow displacement, specifically twice the initial volume, and the same operating conditions were maintained. The permeates of the two stages were collected; the combined permeates were concentrated under vacuum at 0.06 MPa and 45°C to a solid content of 8%, thereby obtaining a clarified extract;

[0132] S5: The clarified extract obtained in S4 is mixed into 0.9% sodium chloride injection at a volume ratio of 1:4, and the mixture is stirred and mixed until the conductivity of the solution stabilizes; the pH of the mixed solution is measured to be 6.0 using a pH meter, and the pH is adjusted to 6.5 by microtitration using injection-grade sodium bicarbonate solution; the pH-adjusted solution is pre-filtered through a 0.45 μm pre-filter membrane to remove visible particles and suspended matter, and then terminally filtered through a 0.22 μm hydrophilic polyethersulfone sterile filter membrane at a temperature of 15° C. and a pressure of 0.08 MPa. The obtained filtrate is an atomized liquid, which is immediately aseptically filled and sealed for later use;

[0133] S6: Take 2 mL of the atomized liquid obtained in S5 and inject it into the liquid storage tank of the medical ultrasonic atomizer, and close the storage tank cover tightly; set the ultrasonic transducer operating frequency to 1.6 MHz and the transducer surface power density to 0.5 W / cm 2 , start the device to form a nebulized aerosol; input medical air with a flow rate of 4L / min into the nebulization chamber of the device, and deliver the generated drug aerosol to the inhalation interface;

[0134] S7: Connect the drug aerosol output by S6 to a disposable oral and nasal mask through a delivery hose, and set the air supply flow rate to 4 L / min; instruct the chronic bronchitis patient to sit at 70 degrees, wear the mask and ensure that it fits the face tightly; the patient performs nebulization inhalation according to the instructions, inhaling through the mouth for 3 seconds during the inhalation phase, holding the breath for 1 second, and exhaling through the nose for 4 seconds. The entire breathing cycle is repeated until all the nebulized liquid is atomized; monitor the remaining drug solution. When it is less than 0.3 mL and the nebulization rate is less than 0.1 mL / min, stop the air supply and remove the mask; after inhalation, instruct the patient to rinse the mouth with 10 mL of sterile water and wipe the inner wall of the mask dry, and then let the device run at no load for 30 seconds to expel residual aerosol;

[0135] S8: After the patient completes three complete courses of nebulized inhalation treatment, each course includes two inhalations per day, and each inhalation of nebulized liquid is approximately equal to 3g of original medicinal material, which lasts for 5 days. The total treatment period is 15 days. The aerosol particle size, inhalation time, breath-holding time and other data are counted, and the patient's lung function improvement indicators are recorded.

[0136] Example 3

[0137] S1: The raw medicinal material of Bangjin Jiao A San was manually cleaned to remove impurities such as sand, branches and leaves, and then cut into 5 cm long segments. The cut medicinal material was placed in a hot air circulation drying oven with a set temperature of 60°C, a relative humidity of 30%, and a wind speed of 0.6 m / s for 8 hours to obtain a preliminary dried material. The dried material was then fed into an air flow ultrafine pulverizer and pulverized at an operating pressure of 0.1.2 MPa. The powder was then graded through a 600 mesh sieve, and the medicinal material powder with a particle size D90 of 25 μm was collected for subsequent extraction operations.

[0138] S2: The medicinal material powder obtained in S1 is placed in the extraction tank of a supercritical CO2 extraction device, and CO2 is pre-pressed to 12 MPa at room temperature; then the extraction temperature is set to 60°C and the extraction pressure is set to 30 MPa, and supercritical CO2 is continuously introduced at a CO2 flow rate of 2.0 L / min, and the extraction is continued for 45 minutes to remove resin and oil impurities; after the extraction is completed, the pressure is reduced to normal pressure at a decompression rate of 10 MPa / min, the discharge valve is opened to remove the residue, and the residue is placed in a vacuum drying oven with a vacuum degree of 0.12 MPa and a temperature of 60°C for 4 hours to obtain purified powder;

[0139] S3: The purified powder obtained in S2 was mixed with deionized water at a material-liquid mass ratio of 1:12, and placed in a sealed extraction tank. The mixture was refluxed and extracted at a temperature of 80°C for 90 minutes to obtain a first extract. The filter residue was refluxed and extracted again with a 30% ethanol solution at a material-liquid ratio of 1:15 for 60 minutes to obtain a second extract. The remaining filter residue was refluxed and extracted with a 70% ethanol solution at a material-liquid ratio of 1:12 for another 45 minutes to obtain a third extract. The three extracts were combined, filtered through a plate and frame to remove suspended matter, and then concentrated under reduced pressure at 60°C and a vacuum degree of 0.09 MPa until the relative density of the extract reached 1.25 to obtain a concentrated extract.

[0140] S4: The concentrated extract obtained in S3 was mixed with sterile purified water in a volume ratio of 1:3, and the viscosity of the solution was adjusted to 50 mPa·s to prepare a pretreated feed solution; the feed solution was transferred to a hollow fiber ultrafiltration membrane module with a molecular weight cutoff of 12 kDa. The operating temperature was set at 35°C, the transmembrane pressure was set at 0.30 MPa, and the circulation flow rate was set at 1.0 m / s. Ultrafiltration was continued until the volume of the retentate decreased to 30% of the initial volume; sterile purified water was then added for tangential flow displacement, specifically 3 times the initial volume, and the same operating conditions were maintained. The permeates of the two stages were collected; the combined permeates were concentrated under vacuum at 0.08 MPa and 55°C to a solid content of 12%, thereby obtaining a clarified extract;

[0141] S5: The clarified extract obtained in S4 is mixed into 0.9% sodium chloride injection at a volume ratio of 1:8, and the mixture is stirred and mixed until the conductivity of the solution stabilizes; the pH of the mixed solution is measured to be 6.0 using a pH meter, and the pH is adjusted to 7.4 by microtitration using injection-grade sodium bicarbonate solution; the pH-adjusted solution is pre-filtered through a 0.45 μm pre-filter membrane to remove visible particles and suspended matter, and then terminally filtered through a 0.22 μm hydrophilic polyethersulfone sterile filter membrane at a temperature of 25° C. and a pressure of 0.12 MPa. The obtained filtrate is an atomized liquid, which is immediately aseptically filled and sealed for later use;

[0142] S6: Take 5 mL of the atomized liquid obtained in S5 and inject it into the liquid storage tank of the medical ultrasonic atomizer, and close the storage tank cover tightly; set the ultrasonic transducer operating frequency to 2.2 MHz and the transducer surface power density to 1.5 W / cm 2 , start the device to form a nebulized aerosol; input medical air with a flow rate of 8L / min into the atomizing chamber of the device, and deliver the generated drug aerosol to the inhalation interface;

[0143] S7: Connect the drug aerosol output by S6 to a disposable oral and nasal mask through a delivery hose, and set the air supply flow rate to 6L / min; instruct the chronic bronchitis patient to sit at 90 degrees, wear the mask and ensure that it fits the face tightly; the patient performs nebulization inhalation according to the instructions, inhaling through the mouth for 5 seconds during the inhalation phase, holding the breath for 2 seconds, and exhaling through the nose for 6 seconds. The entire breathing cycle is repeated until all the nebulized liquid is atomized; monitor the remaining drug solution. When it is less than 0.3mL and the nebulization rate is less than 0.1mL / min, stop the air supply and remove the mask; after inhalation, instruct the patient to rinse the mouth with 20mL of sterile water and wipe the inner wall of the mask dry, and then let the device run at no load for 60 seconds to expel residual aerosol;

[0144] S8: After the patient completes three complete courses of nebulized inhalation treatment, each course includes two inhalations per day, and each inhalation of nebulized liquid is approximately equal to 3g of original medicinal material, which lasts for 5 days. The total treatment period is 15 days. The aerosol particle size, inhalation time, breath-holding time and other data are counted, and the patient's lung function improvement indicators are recorded.

[0145] Comparative Example 1

[0146] S1: Weigh 1.5g of Bangjin Jiao'a powder;

[0147] S2: Add 250 mL of warm water (45–55°C) and stir until fully dissolved or mixed.

[0148] S3: Patients take it orally, twice a day, once in the morning and once in the evening, for 5 consecutive days, with a total treatment period of 15 days.

[0149] Table 2 Comparison of efficacy data

[0150] Comparison Project Example 1 Example 2 Example 3 Comparative Example 1 Improvement of sputum cough score on day 7 (points) 2.8 2.4 2.1 0.9 Cough relief rate on day 10 (%) 93.30％ 86.70％ 82.10％ 45.60％ FEV1 increase (L) 0.42 0.36 0.31 0.12 C-reactive protein decrease (mg / L) 8.5 7.2 6.4 2.3 Inhalation compliance rate (%) 97.60％ 94.20％ 91.50％ 78.00％ Decreased airway inflammation score (points) 3.4 2.9 2.5 1.1 Incidence of adverse reactions (%) 1.20％ 2.30％ 2.90％ 6.70％

[0151] As can be seen from Table 2 above, Example 1 has the best comprehensive performance in treating chronic bronchitis. It is superior to Example 2 and Example 3 in terms of lung function improvement, airway inflammation suppression, symptom relief speed, and patient compliance and safety. It is significantly better than the comparative example 1 of traditional hot water injection. Specifically, the cough relief rate of Example 1 on the 10th day reached 93.3%, FEV1 increased by 0.42L, and C-reactive protein decreased significantly, indicating that systemic inflammation was effectively controlled. In addition, the method improves the drug lung deposition efficiency through atomization, and the patient inhalation compliance rate is as high as 97.6%, which is much higher than the 78.0% of the traditional oral method, and the incidence of adverse reactions is controlled at 1.2%, which is significantly lower than the comparative example. Therefore, the embodiment 1 scheme based on atomization inhalation is the optimal treatment path at present and has good clinical promotion value.

[0152] The criteria for comparing the projects are as follows:

[0153] Improvement in sputum volume score on day 7 (points): Evaluated with reference to the sputum volume grading score in the "Clinical Efficacy Evaluation Standards of Traditional Chinese Medicine for Chronic Bronchitis" using a 0-5 point scale; the improvement is calculated as the difference between before and after treatment;

[0154] Cough relief rate (%) on day 10: assessed based on the Cough VAS questionnaire. A score decrease of ≥2 points or a decrease in daily cough frequency of ≥50% was defined as effective.

[0155] FEV1 improvement (L): Forced expiratory volume in one second (FEV1) was measured using a spirometer (model: MasterScreen PFT, CareFusion); the difference before and after treatment was recorded;

[0156] C-reactive protein decrease (mg / L): serum CRP concentration was measured using immunoturbidimetry (instrument: Beckman AU5800), and the difference before and after treatment was recorded;

[0157] Inhalation compliance rate (%): calculated as the number of inhalations completed by the patient according to the standard twice a day during the 15-day treatment course / total required inhalations × 100%; determined based on the device records and nurse verification results;

[0158] Decrease in airway inflammation score (score): Based on the results of induced sputum examination, the inflammatory cell classification (neutrophils, eosinophils) scoring method is used, with a score of 0 to 4, and the difference before and after treatment is recorded;

[0159] Incidence of adverse reactions (%): According to the "Regulations on Reporting and Monitoring of Adverse Drug Reactions", the number of people experiencing drug-related adverse events such as dry throat, shortness of breath, and nausea / total number of people × 100%.

[0160] The present invention encompasses any alternatives, modifications, equivalents, and solutions that fall within the spirit and scope of the present invention. To provide a thorough understanding of the present invention, specific details are described in detail below in connection with the preferred embodiments of the present invention, but those skilled in the art will be able to fully understand the present invention without these detailed descriptions. Furthermore, to avoid unnecessary confusion regarding the essence of the present invention, well-known methods, processes, procedures, components, and circuits have not been described in detail.

[0161] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for treating chronic bronchitis using the Tibetan medicine Bangjinjiaoa San based on atomization inhalation, characterized in that: The following steps are involved: S1: The Bangjin Jiao A San technical drug is dried at low temperature and then ultrafine ground to obtain technical drug powder; S2: The technical powder obtained in S1 is placed in a supercritical CO2 extraction device to remove resin and oil impurities to obtain purified powder; S3: Using the purified powder as the only raw material, a water-ethanol gradient extraction is performed and the obtained filtrate is concentrated under reduced pressure to obtain a concentrated extract; S4: processing the concentrated extract through an ultrafiltration membrane to remove high molecular weight impurities and obtain a clarified extract; S5: Using normal saline as solvent, prepare the clarified extract into a nebulized solution and perform sterile filtration; S6: The atomized liquid is loaded into a medical ultrasonic atomization device to form a drug aerosol through ultrasonic oscillation; S7: Instruct patients with chronic bronchitis to use a nebulizer inhalation device to inhale the drug aerosol; S8: After completing the entire inhalation treatment course, the inhalation process data is counted and processed to produce a treatment conclusion report.

2. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: Said S1 specifically includes: S11: The raw Bangjin Jiaoasan herbs were manually cleaned to remove sand, branches, and impurities, and then cut into small pieces with a length of 3–5 cm. S12: Place the small segments cut in S11 in a hot air circulation drying oven, control the temperature at 40–60°C, relative humidity ≤30%, and wind speed at 0.3–0.6 m / s, and dry for 4–8 hours to obtain a preliminary dried material; S13: The preliminary dried material is loaded into an airflow ultrafine pulverizer, pulverized using a working air pressure of 0.8–1.2 MPa, and separated through a 600-mesh sieve to collect medicinal material micropowder with a particle size D90 controlled at 10–25 μm.

3. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S2 specifically includes: S21: The medicinal material powder obtained in S1 is placed into an extraction tank of a supercritical CO2 extraction device, and CO2 is pre-pressed to 8MPa–12MPa at room temperature; S22: Under the conditions of temperature 40℃–60℃ and pressure 25MPa–30MPa, supercritical CO2 was introduced with a CO2 flow rate of 1.0L / min–2.0L / min for continuous extraction for 30min–45min; S23: After the extraction is completed, the pressure is reduced to normal pressure at a rate of 5 MPa / min–10 MPa / min, and the discharge valve is opened to remove the residue; S24: The obtained residue is placed in a vacuum drying oven at 50° C.–60° C. and a vacuum degree of 0.08 MPa–0.12 MPa and dried for 2 h–4 h to obtain a purified powder.

4. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S3 specifically includes: S31: Add the purified powder obtained in S2 and deionized water in a material-liquid mass ratio of 1:8 to 1:12 into a sealed extraction tank, reflux and extract at 60°C–80°C for 60–90 minutes, and take the first extract; S32: Filter the first extract and collect the residue, then reflux extract the residue with a 30% ethanol solution at a feed-liquid mass ratio of 1:10 to 1:15 for 40 min–60 min to obtain a second extract at the same temperature range; S33: reflux extraction of the filter residue after the second extraction with a 70% ethanol solution at a feed-liquid mass ratio of 1:8 to 1:12 for 30 min–45 min to obtain a third extract; S34: The extracts from the first, second, and third sections are combined, and after removing suspended solids through a plate and frame filter, they are concentrated under reduced pressure at 50°C–60°C and a vacuum degree of 0.08 MPa–0.09 MPa until the relative density of the extract reaches 1.10–1.25 to obtain a concentrated extract.

5. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S4 specifically includes: S41: The concentrated extract obtained in S3 is added to sterile purified water in a volume ratio of 1:1 to 1:3, and the viscosity of the solution is adjusted to 30-50 mPa·s to obtain a pretreated solution; S42: The pretreated liquid is transported to a hollow fiber ultrafiltration membrane module equipped with a molecular weight cutoff of 8 kDa–12 kDa, and ultrafiltration is performed at a temperature of 25°C–35°C, a transmembrane pressure of 0.15 MPa–0.30 MPa, and a circulation flow rate of 0.5 m / s–1.0 m / s. The operation is continued until the volume of the retentate is 20%–30% of the initial volume; S43: Sterile purified water is continuously added to the ultrafiltration system for tangential flow displacement. The displacement water volume is 2–3 times the initial feed volume. The same operating conditions as S42 are maintained and the permeate is collected. S44: The permeates obtained in S42 and S43 are combined and concentrated under vacuum conditions of 0.06 MPa-0.08 MPa and a temperature of 45° C.-55° C. to a solid content of 8%-12% to obtain the clarified extract.

6. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S5 specifically includes: S51: introducing the clarified extract obtained in S4 into 0.9% sodium chloride injection at a volume ratio of 1:4 to 1:8, and mixing while stirring until the conductivity of the solution stabilizes; S52: Measure the pH of the resulting mixture using a pH meter and adjust the pH to 6.5–7.4 by microtitration using injection-grade sodium bicarbonate solution; S53: Pre-filter the pH-adjusted mixed solution through a 0.45 μm pre-filter membrane to remove visible particles and suspended matter; S54: The pre-filtered solution is continuously filtered through a 0.22 μm pore size hydrophilic polyethersulfone sterile filter membrane at a temperature of 15°C–25°C and a pressure of 0.08 MPa–0.12 MPa for terminal filtration, and the filtrate is collected as the atomized liquid; S55: The obtained atomized liquid is aseptically filled and sealed for later use.

7. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S6 specifically includes: S61: Sample the atomized liquid obtained in S5 at a volume of 2 mL–5 mL per treatment and inject it into the liquid storage tank of the medical ultrasonic atomizer, and then tightly close the storage tank cap; S62: Set the ultrasonic transducer operating frequency to 1.6MHz–2.2MHz and the transducer surface power density to 0.5W / cm 2 –1.5W / cm 2 , starting the device to generate an initial atomized aerosol; S63: Input medical air at a flow rate of 4 L / min–8 L / min into the atomizing chamber of the atomizing device, and output the aerosol to the inhalation port; S64: Real-time measurement of the aerosol mass median particle size. When the measured value exceeds the range of 2μm–5μm, adjust the ultrasonic power or airflow rate until the particle size falls back into the range.

8. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S7 specifically includes: S71: Connect the drug aerosol delivery tube output by S6 to the disposable oral and nasal mask and set the air supply flow rate to 4L / min–6L / min; S72: Have the chronic bronchitis patient sit in a 70°–90° position, put on the mask, ensure that the edge of the mask completely fits the face, and start the nebulizer inhalation device; S73: Instruct the patient to cycle through the mouth for 3–5 seconds of constant inhalation, breath holding for 1–2 seconds, and nasal exhalation for 4–6 seconds until all the nebulized liquid is atomized. S74: When the remaining liquid volume in the nebulizer drops to 0.3 mL and the nebulization rate is lower than 0.1 mL / min, stop the gas supply and remove the mask; S75: After inhalation, instruct the patient to rinse the mouth with 10 mL–20 mL of sterile water and wipe the inner wall of the mask dry, then run the device idling for 30 s–60 s to expel residual aerosol.

9. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S8 specifically includes: S81: After the patient completes three consecutive complete courses of nebulized inhalation therapy, each course includes two inhalations per day, each inhalation of nebulized liquid is approximately equal to 3g of the original medicinal material, for 5 days, and the total treatment period is 15 days; S82: Collect the patient's nebulization inhalation records during each treatment course, including the duration of each inhalation, the amount of nebulized liquid used, the respiratory rate, and the inhalation-exhalation ratio, and form a treatment course inhalation database; S83: Within 72 hours after the third course of treatment, the cough symptom score, sputum volume score, and serum C-reactive protein concentration of the patients were evaluated, and the pre-treatment and post-treatment values ​​of the three indicators were recorded; S84: Calculate the improvement rate of each indicator using a standardized algorithm, compare the improvement rate result with a preset statistical template, and confirm whether it meets the set change range; S85: Based on the data obtained from S82 and S84, a structured treatment conclusion report is generated, which includes the changing trends of various indicators, the statistics of compliance during the inhalation process, and the final grading evaluation results of the treatment effect.

10. The method for treating chronic bronchitis with the Tibetan medicine Bangjinjiaoa San based on atomization inhalation according to claim 1, characterized in that: The S84 specifically includes: S841: Import the pre-treatment value and post-treatment value of each indicator obtained in S83 into the data processing module to unify the numerical precision and measurement unit; S842: Calculate the improvement rate R for the i-th indicator according to the following formula i , the formula is: Where V pre,i is the value before treatment, V post,i The calculated value is the post-treatment value, and the calculation result is rounded to one decimal place; S843: The improvement rate R of each indicator i The corresponding indicator target interval [α i , β i ] to compare; if R i <α i , then the record evaluation level is not up to standard; if α i ≤R i ≤β i , record as meeting the standard; if R i >β i , recorded as significantly achieved, where α i and β i are the lowest and highest points of the target range respectively.

Images