A manufacturing process and equipment for a traditional Chinese medicine nebulizer for treating respiratory infections.

Abstract

This invention discloses a process and equipment for preparing a traditional Chinese medicine nebulizer for treating respiratory infections, belonging to the field of pharmaceutical preparation technology. The invention includes step a: adding Houttuynia cordata and Lonicera japonica at a mass ratio of 2-2.5:1-1.5 into a multifunctional extraction tank, adding 2-10 times the weight of purified water and 0.1%-1% of cellulase by weight of the herbs, and incubating at 30-60℃ for 1-2 hours to enzymatically hydrolyze the herbs, thereby destroying the cell wall structure. This invention effectively destroys the cell wall structure of Houttuynia cordata and Lonicera japonica by introducing cellulase for enzymatic pretreatment before extraction, allowing for the full release of volatile active ingredients such as methyl nonyl ketone and houttuynin within the cells. Simultaneously, it shortens distillation time, reduces energy consumption, and improves the utilization rate of the herbs. Hydroxypropyl β-cyclodextrin is used to encapsulate the volatile active ingredients in the redistilled liquid, forming stable inclusion complexes that effectively inhibit component volatilization and oxidative degradation, improving the stability of the preparation.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to a process and equipment for preparing a traditional Chinese medicine nebulizer for treating respiratory infections. Background Technology

[0002] Respiratory infections are common clinical diseases, including acute upper respiratory tract infections, bronchitis, and pneumonia, and their incidence ranks among the highest of all diseases. Traditional Chinese medicine nebulized inhalation therapy, as an important treatment for respiratory diseases, has significant advantages such as direct drug delivery to the lesion, rapid onset of action, high local drug concentration, and few systemic side effects, and has received widespread attention in recent years.

[0003] Houttuynia cordata Thunb., a plant belonging to the genus Houttuynia in the Saururaceae family, is pungent and slightly cold in nature, and enters the lung meridian. It has the effects of clearing heat and detoxifying, reducing swelling and draining pus, and promoting diuresis. Modern pharmacological studies have shown that its main active ingredients are volatile components such as methyl nonyl ketone and houttuynin, which have inhibitory effects on various pathogenic microorganisms such as Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Lonicera japonica Thunb., the dried flower bud of a plant in the Caprifoliaceae family, is sweet and cold in nature, and has the effects of clearing heat and detoxifying, and dispersing wind-heat. Its main active ingredients are chlorogenic acid and luteolin, which have broad-spectrum antibacterial, antiviral, and immunomodulatory effects. The combination of these two herbs synergistically enhances their antibacterial and antiviral effects, and is hailed as a "typical representative of traditional Chinese medicine antibiotics."

[0004] However, the existing preparation processes for fish and honeysuckle atomized formulations have the following technical defects: First, when extracting volatile oils using traditional steam distillation, the dense cell wall structure of the medicinal materials results in low dissolution efficiency of the active ingredients, leading to insufficient utilization of the medicinal materials, long distillation time, and high energy consumption. Second, the main active ingredients in houttuynia cordata and honeysuckle, such as methyl nonyl ketone and houttuynin, are volatile substances that are prone to oxidative degradation or volatilization loss during distillation extraction and subsequent storage, resulting in poor formulation stability and decreased content of active ingredients. Third, existing processes mostly use traditional filtration methods, which are difficult to effectively remove minute impurities, tannins, and macromolecular substances from the extract, resulting in poor formulation clarity and easy precipitation during long-term storage, affecting the safety of clinical use. Fourth, the atomizing agent acts directly on the respiratory mucosa and has strict requirements for osmotic pressure. The existing processes use crude isotonic adjustment methods, and the compatibility of the formulation with the respiratory mucosa needs to be improved.

[0005] To address these issues, we provide a process and equipment for manufacturing a traditional Chinese medicine nebulizer for treating respiratory infections. Summary of the Invention

[0006] The purpose of this invention is to provide a process and equipment for manufacturing a traditional Chinese medicine nebulizer for treating respiratory system infections. By combining enzymatic extraction, cyclodextrin inclusion stabilization, membrane filtration purification, and isotonic optimization adjustment, the invention solves the problems of low extraction rate of effective components, easy loss of volatile components, poor clarity of the preparation, and crude isotonic adjustment in the prior art.

[0007] To solve the above-mentioned technical problems, the present invention is achieved through the following technical solution: This invention relates to a process for preparing a traditional Chinese medicine nebulizer for treating respiratory infections, comprising the following steps: Step a: Houttuynia cordata and Lonicera japonica are added to a multifunctional extraction tank at a mass ratio of 2-2.5:1-1.5, along with 2-10 times the weight of purified water and 0.1%-1% of cellulase by weight of the herbs. The mixture is incubated at 30-60°C for 1-2 hours to enzymatically hydrolyze the herbs, thereby disrupting the cell wall structure and promoting the release of active ingredients; Step b: After enzymatic hydrolysis, the mixture is extracted by steam distillation or co-distillation, collecting a primary distillate equivalent to 1-5 times the total weight of the herbs; Step c: The primary distillate is transferred to a distillation apparatus for redistillation, and the redistilled liquid is collected. The volume is 0.1 to 0.8 times the total weight of the medicinal materials; Step d: Add 0.3% to 3% sodium chloride by weight of the redistilled liquid for isotonic adjustment, and simultaneously add 1% to 5% hydroxypropyl β-cyclodextrin by weight of the redistilled liquid. Stir and encapsulate at 40 to 60°C for 1 to 3 hours to allow the volatile active ingredients to form an inclusion complex; Step e: After encapsulation, cool the liquid to room temperature and filter it using a membrane filtration system, which includes a microfiltration membrane with a pore size of 0.22 to 0.45 μm; Step f: Fill the filtered liquid under aseptic conditions; Step g: Sterilize the filled preparation to obtain the finished traditional Chinese medicine nebulizer for treating respiratory system infections.

[0008] The present invention is further configured such that, in step a, the amount of cellulase added is 0.3% to 0.8% of the weight of the medicinal material, the enzymatic hydrolysis temperature is 40 to 50°C, and the enzymatic hydrolysis time is 1.5 to 2 hours.

[0009] The present invention is further configured such that, in step b, the steam pressure of the steam distillation method is 0.05-0.15 MPa and the distillation time is 2-4 hours; the amount of water added in the co-water distillation method is 4-8 times the weight of the medicinal material and the distillation time is 3-5 hours.

[0010] The present invention is further configured such that, in step c, the steam pressure of redistillation is 0.02 to 0.08 MPa, and the temperature of the collected redistilled liquid is 40 to 60°C.

[0011] The present invention is further configured such that, in step d, the amount of sodium chloride added is 0.8% to 2% of the weight of the redistilled liquid, the amount of hydroxypropyl β-cyclodextrin added is 1% to 4% of the weight of the redistilled liquid, and the stirring speed is 60 to 120 r / min.

[0012] The present invention is further configured such that, in step d, before adding hydroxypropyl β-cyclodextrin, the hydroxypropyl β-cyclodextrin is first dissolved in a small amount of water for injection to prepare a solution with a mass concentration of 10% to 20%, and then slowly added to the redistilled solution.

[0013] The present invention is further configured such that, in step e, the membrane filtration system can employ two-stage filtration, with the first stage being a polyethersulfone microfiltration membrane with a pore size of 0.45 μm and the second stage being a polyethersulfone microfiltration membrane with a pore size of 0.22 μm, and the filtration pressure being 0.1–0.3 MPa.

[0014] The present invention is further configured such that, in step e, before membrane filtration, the feed liquid is first coarsely filtered through a pre-filtration device with a pore size of 1 to 5 μm to remove large particulate impurities.

[0015] The present invention is further configured such that, in step f, the filling environment is a Class 100 clean area, and the drug solution is protected by nitrogen before filling.

[0016] An apparatus for manufacturing a traditional Chinese medicine nebulizer for treating respiratory infections includes a multifunctional extraction tank, a distillation device, a membrane filtration system, and an injection filling and sealing device connected sequentially by pipelines. The injection filling and sealing device includes a bottle washing machine, a dryer, and a filling and sealing machine.

[0017] The present invention has the following beneficial effects: This invention introduces cellulase for enzymatic pretreatment before extraction, effectively disrupting the cell wall structure of Houttuynia cordata and Lonicera japonica, allowing for the full release of volatile active ingredients such as methyl nonyl ketone and houttuynin within the cells. Simultaneously, it shortens distillation time, reduces energy consumption, and improves the utilization rate of medicinal materials. Hydroxypropyl β-cyclodextrin is used to encapsulate the volatile active ingredients in the redistilled liquid, forming stable inclusion complexes that effectively inhibit component volatilization and oxidative degradation, thus improving the stability of the formulation.

[0018] This invention achieves efficient preparation of traditional Chinese medicine nebulizers for treating respiratory infections through an integrated process of enzymatic pretreatment, distillation extraction, redistillation purification, isotonic inclusion, membrane filtration, and filling and sterilization. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below.

[0020] Figure 1A schematic diagram of a multifunctional extraction tank in the manufacturing process and equipment for a traditional Chinese medicine nebulizer for treating respiratory infections; Figure 2 A schematic diagram of a distillation device in the manufacturing process and equipment of a traditional Chinese medicine nebulizer for treating respiratory infections; Figure 3 This is a schematic diagram of a membrane filtration system in the manufacturing process and equipment of a traditional Chinese medicine nebulizer for treating respiratory infections. Figure 4 A schematic diagram of a bottle washing machine for injection filling and sealing equipment in the manufacturing process and equipment of a traditional Chinese medicine nebulizer for treating respiratory infections; Figure 5 A schematic diagram of a dryer for injection filling equipment in a process and equipment for manufacturing a traditional Chinese medicine nebulizer for treating respiratory infections; Figure 6 This is a schematic diagram of a filling and sealing machine for an injection filling and sealing device in a process and equipment for manufacturing a traditional Chinese medicine nebulizer for treating respiratory infections.

[0021] In the attached diagram: 100, multi-functional extraction tank; 200, distillation apparatus; 300, membrane filtration system; 400, bottle washing machine; 500, dryer; 600, filling and sealing machine. Detailed Implementation

[0022] The technical solutions of the present invention will be described below with reference to the accompanying drawings. The described embodiments are only some embodiments of the present invention, and not all embodiments.

[0023] Please see Figure 1-6A process for preparing a traditional Chinese medicine nebulizer for treating respiratory infections includes the following steps: Step a: Houttuynia cordata and honeysuckle are added to a multifunctional extraction tank 100 at a mass ratio of 2-2.5:1-1.5, purified water is added at 2-10 times the weight of the herbs, and cellulase is added at 0.1%-1% of the weight of the herbs. The mixture is kept at 30-60℃ for 1-2 hours to enzymatically hydrolyze the herbs, thereby destroying the cell wall structure and promoting the release of active ingredients. Preferably, the amount of cellulase added is 0.3%–0.8% of the weight of the medicinal material, the enzymatic hydrolysis temperature is 40–50℃, and the enzymatic hydrolysis time is 1.5–2 hours; Step b: After enzymatic hydrolysis, distillation extraction is carried out by steam distillation or co-distillation, and the initial distillate equivalent to 1–5 times the weight of the medicinal material is collected. The steam pressure of steam distillation is 0.05–0.15 MPa, and the distillation time is 2–4 hours; the amount of water added in co-distillation is 4–8 times the weight of the medicinal material, and the distillation time is 3–5 hours; Step c: The initial distillate is transferred to distillation apparatus 200 for further processing. Redistill, collect the redistilled liquid. The volume of the redistilled liquid should be 0.1–0.8 times the total weight of the medicinal materials. The steam pressure of the redistillation should be 0.02–0.08 MPa, and the temperature of the collected redistilled liquid should be 40–60℃. Step d: Add 0.3%–3% sodium chloride by weight of the redistilled liquid for isotonic adjustment, and simultaneously add 0.5%–5% hydroxypropyl β-cyclodextrin by weight of the redistilled liquid. Stir and infuse at 40–60℃ for 1–3 hours to allow the volatile active ingredients to form inclusion complexes. The amount of sodium chloride added should be 0.8%–2% by weight of the redistilled liquid. The amount of hydroxypropyl β-cyclodextrin added is 2% to 4% of the weight of the redistilled liquid, and the stirring speed is 60 to 120 r / min. Before adding hydroxypropyl β-cyclodextrin, it is first dissolved in a small amount of injection water to prepare a solution with a mass concentration of 10% to 20%, and then slowly added to the redistilled liquid; Step e: After the inclusion is completed, the solution is cooled to room temperature and filtered using a membrane filtration system 300. The membrane filtration system 300 includes a microfiltration membrane with a pore size of 0.22 to 0.45 μm. The membrane filtration system 300 can adopt a two-stage filtration, the first stage being... The first stage uses a polypropylene microfiltration membrane with a pore size of 0.45 μm, and the second stage uses a polyethersulfone microfiltration membrane with a pore size of 0.22 μm. The filtration pressure is 0.1–0.3 MPa. Alternatively, only one type of filter membrane can be used. Before membrane filtration, the liquid is first coarsely filtered through a pre-filtration device with a pore size of 1–5 μm to remove large particulate impurities. Step f: The filtered liquid is filled under aseptic conditions in a Class 100 cleanroom. The liquid is protected with nitrogen before filling. Step g: The filled preparation is sterilized to obtain the finished traditional Chinese medicine nebulizer for treating respiratory infections.

[0024] An integrated process, encompassing enzymatic pretreatment, distillation extraction, redistillation purification, isotonic inclusion, membrane filtration, and filling sterilization, has enabled the efficient preparation of a traditional Chinese medicine nebulizer for treating respiratory infections. The enzymatic hydrolysis step utilizes cellulase to disrupt the cell wall structure of Houttuynia cordata and Lonicera japonica, allowing for the full release of volatile active ingredients. This significantly improves the extraction rate and shortens the distillation time compared to traditional direct distillation. Hydroxypropyl β-cyclodextrin inclusion technology effectively inhibits the volatilization and oxidative degradation of volatile components, improving formulation stability. A 300-layer membrane filtration system precisely removes impurities and microorganisms, ensuring clarity and safety. Sodium chloride isotonic adjustment reduces respiratory mucosal irritation, improving user comfort. The multi-functional extraction tank 100, distillation device 200, membrane filtration system 300, and filling equipment are sequentially connected via pipelines to form a closed, continuous production line, reducing the risk of cross-contamination and making it suitable for large-scale industrial production.

[0025] The amount of cellulase added is further limited to 0.3% to 0.8% of the weight of the medicinal material, the enzymatic hydrolysis temperature is optimized to 40 to 50°C, and the enzymatic hydrolysis time is extended to 1.5 to 2 hours. This allows the cellulase to maintain high activity at a suitable temperature, resulting in more complete enzymatic destruction of the cell wall and further improving the release efficiency of the active ingredients. At the same time, it avoids enzyme inactivation and energy waste caused by excessive enzyme amount or excessive temperature.

[0026] The study clarified that the steam pressure for steam distillation is 0.05–0.15 MPa and the distillation time is 2–4 hours, while the water addition for co-water distillation is 4–8 times the weight of the medicinal material and the distillation time is 3–5 hours. This provides precise process parameter windows for different distillation methods, ensuring that the distillation process is stable and controllable, maximizing the extraction rate of effective components, and avoiding component damage or incomplete distillation due to excessively high steam pressure.

[0027] The steam pressure of redistillation is limited to 0.02–0.08 MPa, and the temperature of the collected redistillate is controlled at 40–60 °C. Secondary purification is carried out under lower pressure and suitable temperature, which avoids the destruction of heat-sensitive active ingredients by high temperature, and achieves effective concentration and purification of the initial distillate, thereby improving the purity and content of active ingredients in the formulation.

[0028] The amount of sodium chloride added was optimized to 0.8%–2% of the weight of the redistilled liquid, and the amount of hydroxypropyl β-cyclodextrin added was optimized to 2%–4%. The stirring speed was controlled at 60–120 r / min, so that the osmotic pressure of the formulation was closer to the physiological isotonic requirement, the inclusion effect was more complete and uniform, and the comfort of patients' nebulized inhalation and the physicochemical stability of the formulation were improved.

[0029] Before adding hydroxypropyl β-cyclodextrin, the cyclodextrin is first prepared into a solution with a mass concentration of 10% to 20% and then added slowly. This avoids the problem of incomplete inclusion or aggregation and precipitation caused by excessively high local concentration when the cyclodextrin powder is added directly. This makes the inclusion reaction more uniform and complete, and improves the inclusion rate and the uniformity of the formulation.

[0030] A two-stage membrane filtration system 300 is adopted. The first stage uses a 0.45μm polyethersulfone microfiltration membrane to remove larger particulate impurities, and the second stage uses a 0.22μm polyethersulfone microfiltration membrane to finely filter and remove tiny particles and microorganisms. The filtration pressure is controlled at 0.1-0.3MPa, which realizes gradient precision filtration, protects the fine filtration membrane and extends the membrane's service life, and ensures that the formulation meets the clarity requirements for injection.

[0031] A pre-filtration device with a pore size of 1-5 μm is added before membrane filtration to perform coarse filtration, which removes large particulate impurities, medicinal material fragments and colloidal flocs from the extract in advance. This effectively reduces the filtration load on the subsequent microfiltration membrane, prevents membrane pore blockage, improves membrane filtration flux and continuous production efficiency, and reduces membrane replacement frequency and production costs.

[0032] The filling environment is limited to a Class 100 clean area, and the drug solution is protected by nitrogen before filling. The Class 100 clean environment minimizes the risk of microbial and particulate contamination, and the nitrogen treatment effectively isolates oxygen and prevents the oxidative degradation of volatile active ingredients. This ensures the sterility level and long-term stability of the formulation from both the production environment and packaging process perspectives.

[0033] An apparatus for manufacturing a traditional Chinese medicine nebulizer for treating respiratory infections includes a multifunctional extraction tank 100, a distillation device 200, a membrane filtration system 300, and an injection filling and sealing device connected sequentially by pipes. The injection filling and sealing device includes a bottle washing machine 400, a dryer 500, and a filling and sealing machine 600.

[0034] The multi-functional extraction tank 100, distillation device 200, membrane filtration system 300 and injection filling equipment are connected sequentially through pipelines to form a fully enclosed continuous production line. This reduces the number of times materials are transferred between processes in traditional processes, lowers the risk of microbial contamination and component volatilization, improves production efficiency, and realizes integrated, automated and large-scale industrial production of Chinese medicine atomizing agents from extraction to filling. Example

[0035] Take 4000g of Houttuynia cordata and 2000g of Lonicera japonica, and put them into the multi-functional extraction tank 1001 through the feeding port 5. Add 60000mL of purified water and add 18g of cellulase (0.3% of the weight of the herbs) through the enzyme addition port 19. Turn on the stirring device 8 and keep it at 45℃ for 1.5 hours for enzymatic hydrolysis. After the enzymatic hydrolysis is completed, steam is introduced through the steam inlet 6 and the steam pressure is controlled at 0.08MPa for steam distillation. Collect 18000mL of the initial distillate (equivalent to 3 times the total weight of the herbs). The initial distillate is condensed by the condenser 20 and enters the initial distillation receiving tank 10. Transfer the initial distillate from the initial distillation receiving tank 10 to the distillation device 2002 for redistillation. The steam pressure is controlled at 0.05MPa. Collect 1000mL of the redistilled liquid (equivalent to 0.17 times the total weight of the herbs). The temperature of the redistilled liquid is 50℃. After condensation, it enters the redistilled receiving tank 11.

[0036] Add 12g of sodium chloride (1.2% of the redistilled liquid weight) and 30g of hydroxypropyl β-cyclodextrin (3% of the redistilled liquid weight) to the redistilled liquid in the receiving tank 11. The hydroxypropyl β-cyclodextrin is pre-prepared as a 15% aqueous solution. Stir and encapsulate the solution at 80 rpm for 2 hours at 50°C. After encapsulation, cool the solution to room temperature and first perform coarse filtration through a pre-filter 12 (3μm pore size), followed by two-stage filtration through a microfiltration membrane assembly 13. The first stage is a polyethersulfone microfiltration membrane with a pore size of 0.45μm, and the second stage is a polyethersulfone microfiltration membrane with a pore size of 0.22μm. The filtration pressure is 0.2MPa. The filtered solution enters the storage tank 14 and is filled in a Class 100 cleanroom environment using a metering pump 15 and a filling head 16. The filling specification is 2mL / vial. The solution is protected with nitrogen before filling. After being filled and sealed, the preparation is placed in a sterilizer and sterilized with circulating steam at a temperature of 100°C for 30 minutes to obtain the finished product of the traditional Chinese medicine nebulizer for treating respiratory infections. Example

[0037] Take 3000g of Houttuynia cordata and 1500g of Lonicera japonica, and put them into the multi-functional extraction tank 1001 through the feeding port 5. Add 36000mL of purified water and add 13.5g of cellulase (0.3% of the weight of the herbs) through the enzyme addition port 19. Turn on the stirring device 8 and incubate at 40℃ for 2 hours for enzymatic hydrolysis. After enzymatic hydrolysis, add 27000mL of purified water (6 times the total weight of the herbs) and distill using the co-aqueous distillation method for 4 hours. Collect 12000mL of the initial distillate (equivalent to 2.7 times the total weight of the herbs). After condensing the initial distillate through the condenser 20, the initial distillate enters the initial distillation receiving tank 10. Transfer the initial distillate from the initial distillation receiving tank 10 to the distillation apparatus 2002 for redistillation. Control the steam pressure at 0.06MPa and collect 2250mL of the redistilled liquid (equivalent to 0.5 times the total weight of the herbs). The temperature of the redistilled liquid is 45℃. After condensation, the liquid enters the redistilled liquid receiving tank 11.

[0038] 27g of sodium chloride (1.2% of the redistilled liquid weight) and 67.5g of hydroxypropyl β-cyclodextrin (3% of the redistilled liquid weight) were added to the redistilled liquid in the receiving tank 11. The hydroxypropyl β-cyclodextrin was pre-prepared as a 12% aqueous solution. The mixture was stirred at 100 rpm for 2.5 hours at 45°C. After encapsulation, the solution was cooled to room temperature and first coarsely filtered through a pre-filter 12 (5μm pore size), then subjected to two-stage filtration through a microfiltration membrane assembly 13. The first stage was a polyethersulfone microfiltration membrane with a pore size of 0.45μm, and the second stage was a polyethersulfone microfiltration membrane with a pore size of 0.22μm. The filtration pressure was 0.15MPa. The filtered solution entered the storage tank 14 and was filled in a Class 100 cleanroom environment using a metering pump 15 and a filling head 16. The filling volume was 5mL / vial. The solution was protected with nitrogen before filling. After being filled and sealed, the preparation is placed in a sterilizer and sterilized by autoclaving at a temperature of 121°C for 15 minutes to obtain the finished product of the traditional Chinese medicine nebulizer for treating respiratory infections. Example

[0039] Take 5000g of Houttuynia cordata and 2500g of Lonicera japonica, and put them into the multi-functional extraction tank 1001 through the feeding port 5. Add 75000mL of water for injection, and add 75g of cellulase (1% of the weight of the medicinal materials) through the enzyme addition port 19. Turn on the stirring device 8 and keep it at 50℃ for 1 hour for enzymatic hydrolysis. After the enzymatic hydrolysis is completed, steam is introduced through the steam inlet 6, and the steam pressure is controlled at 0.12MPa for steam distillation. Collect 22500mL of the initial distillate (equivalent to 3 times the total weight of the medicinal materials). The initial distillate is condensed by the condenser 20 and enters the initial distillation receiving tank 10. Transfer the initial distillate from the initial distillation receiving tank 10 to the distillation device 2002 for redistillation. The steam pressure is controlled at 0.04MPa. Collect 6000mL of the redistilled liquid (equivalent to 0.8 times the total weight of the medicinal materials). The temperature of the redistilled liquid is 55℃. After condensation, it enters the redistilled receiving tank 11.

[0040] Add 120g of sodium chloride (2% of the redistilled liquid weight) and 300g of hydroxypropyl β-cyclodextrin (5% of the redistilled liquid weight) to the redistilled liquid in the receiving tank 11. The hydroxypropyl β-cyclodextrin is pre-prepared as a 20% aqueous solution. Stir and encapsulate the solution at 55°C and 60r / min for 1 hour. After encapsulation, cool the solution to room temperature and first perform coarse filtration through a pre-filter 12 (1μm pore size), followed by two-stage filtration through a microfiltration membrane assembly 13. The first stage is a polyethersulfone microfiltration membrane with a pore size of 0.45μm, and the second stage is a polyethersulfone microfiltration membrane with a pore size of 0.22μm. The filtration pressure is 0.25MPa. The filtered solution enters the storage tank 14 and is filled in a Class 100 cleanroom environment using a metering pump 15 and a filling head 16. The filling specification is 2mL / vial. The solution is protected with nitrogen before filling. After being filled and sealed, the preparation is placed in a sterilizer and sterilized with circulating steam at a temperature of 100°C for 30 minutes to obtain the finished product of the traditional Chinese medicine nebulizer for treating respiratory infections.

[0041] The preferred embodiments of the present invention disclosed above are only for the purpose of illustrating the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific implementation described herein. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can better understand and utilize the present invention.

Claims

1. A manufacturing process for a traditional Chinese medicine nebulizer for treating respiratory infections, characterized in that: Includes the following steps: Step a: Put houttuynia cordata and honeysuckle into a multi-functional extraction tank at a mass ratio of 2-2.5:1-1.5, add 2-10 times the weight of the herbs in purified water, add 0.1%-1% of the weight of the herbs in cellulase, and incubate at 30-60℃ for 1-2 hours to decompose the cell wall structure of the herbs and promote the release of active ingredients. Step b: After enzymatic hydrolysis, distillation extraction is carried out by steam distillation or co-water distillation, and the initial distillate equivalent to 1 to 5 times the total weight of the medicinal materials is collected. Step c: Transfer the initial distillate to a distillation apparatus for redistillation, and collect the redistilled liquid. The volume of the redistilled liquid is 0.1 to 0.8 times the total weight of the medicinal materials. Step d: Add 0.3% to 3% sodium chloride by weight of the redistilled liquid to adjust to isotonicity, and simultaneously add 0.5% to 5% hydroxypropyl β-cyclodextrin by weight of the redistilled liquid. Stir and incorporate at 40 to 60°C for 1 to 3 hours to allow the volatile active ingredients to form inclusion complexes. Step e: After the encapsulation is completed, the liquid is cooled to room temperature and filtered using a membrane filtration system, which includes a microfiltration membrane with a pore size of 0.22 to 0.45 μm. Step f: Fill and seal the filtered drug solution under aseptic conditions; Step g: Sterilize the filled preparation to obtain the finished Chinese medicine nebulizer for treating respiratory infections.

2. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step a, the amount of cellulase added is 0.3% to 0.8% of the weight of the medicinal material, the enzymatic hydrolysis temperature is 40 to 50°C, and the enzymatic hydrolysis time is 1.5 to 2 hours.

3. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step b, the steam pressure of the steam distillation method is 0.05-0.15 MPa, and the distillation time is 2-4 hours; the water added in the co-water distillation method is 4-8 times the weight of the medicinal material, and the distillation time is 3-5 hours.

4. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step c, the steam pressure of redistillation is 0.02–0.08 MPa, and the temperature of the collected redistilled liquid is 40–60 °C.

5. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step d, the amount of sodium chloride added is 0.8% to 2% of the weight of the redistilled liquid, the amount of hydroxypropyl β-cyclodextrin added is 2% to 4% of the weight of the redistilled liquid, and the stirring speed is 60 to 120 r / min.

6. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step d, before adding hydroxypropyl β-cyclodextrin, the hydroxypropyl β-cyclodextrin is first dissolved in a small amount of water for injection to prepare a solution with a mass concentration of 10% to 20%, and then slowly added to the redistilled solution.

7. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step e, the membrane filtration system can employ two-stage filtration: the first stage is a polyethersulfone microfiltration membrane with a pore size of 0.45 μm, and the second stage is a polyethersulfone microfiltration membrane with a pore size of 0.22 μm, with a filtration pressure of 0.1–0.3 MPa.

8. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step e, before membrane filtration, the feed liquid is first coarsely filtered through a pre-filtration device with a pore size of 1-5 μm to remove large particulate impurities.

9. The manufacturing process of a traditional Chinese medicine nebulizer for treating respiratory infections according to claim 1, characterized in that: In step f, the filling environment is a Class 100 clean area, and the drug solution is protected by nitrogen before filling.

10. The apparatus for preparing a traditional Chinese medicine nebulizer for treating respiratory infections according to any one of claims 1-9, characterized in that: It includes a multi-functional extraction tank, a distillation device, a membrane filtration system, and an injection filling and sealing device connected in sequence by pipelines. The injection filling and sealing device includes a bottle washing machine, a dryer, and a filling and sealing machine.

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