Laryngology blowing sore powder and its preparation method and application
By designing a three-stage sustained-release microsphere structure, the problem of short retention time of traditional throat sprays at the oral ulcer site was solved, achieving targeted retention and graded release of the drug, improving drug utilization and medication compliance, and promoting ulcer healing.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SUZHOU TRADITIONAL CHINESE MEDICINE HOSPITAL
- Filing Date
- 2026-04-28
- Publication Date
- 2026-07-24
AI Technical Summary
Traditional throat sprays have a short retention time at the site of oral ulcers, low bioavailability, and rapid drug loss, requiring frequent administration and resulting in poor medication adherence and difficulty in guaranteeing efficacy.
The device employs a three-tiered sustained-release microsphere structure. The inner layer consists of a modified hydroxyapatite-calcined borax composite microcore loaded with Fritillaria cirrhosa, Typha pollen, and Angelica dahurica. The middle layer is an enzyme-responsive methacrylamide gelatin/poly-ε-caprolactone dual-network composite gel loaded with Phellodendron chinense, Coptis chinensis, human placenta extract, and artificial bezoar. The outer layer consists of chitosan quaternary ammonium salt microneedles infused with menthol. By extending the retention time through physical anchoring and electrostatic adsorption, and combining enzyme response and sustained-release mechanisms, the device achieves targeted retention and graded release of the drug.
It significantly improved the drug's retention time at the ulcer site and its utilization rate, achieving rapid analgesia, anti-inflammation, and promotion of mucosal healing, thus improving medication adherence and drug utilization.
Smart Images
Figure FT_1 
Figure FT_2 
Figure FT_3
Abstract
Description
Technical Field
[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a throat-related inhalation powder, its preparation method, and its application. Background Technology
[0002] Oral ulcers are common, recurrent ulcerative lesions of the oral mucosa, clinically manifesting as round or oval, painful ulcers on the mucosal surface, severely affecting patients' eating, speech, and quality of life. Their etiology is complex, related to multiple factors such as local trauma, immune dysregulation, infection, and trace element deficiency. Current clinical treatment primarily involves topical medications to reduce inflammation, relieve pain, prevent secondary infection, and promote mucosal repair.
[0003] Among numerous topical drug delivery formulations, inhaled powders (medicated sprays) hold unique value in traditional Chinese medicine's laryngology and modern oral mucosal disease treatment due to their advantages such as direct targeting of ulcer sites and ease of use. Traditional and existing laryngological inhaled powders are mostly made by directly mixing fine powders obtained from pulverizing and sieving raw Chinese medicinal materials, or by adding a small amount of modern drug extract powder. When used, the medication is blown onto the ulcer surface using a powder sprayer.
[0004] However, these traditional powdered medications suffer from a long-standing, unresolved core technical flaw: extremely short drug retention time at the ulcer target site, resulting in low bioavailability. The oral cavity is a dynamic, moist environment with continuous saliva secretion, swallowing, and tongue movement. When the powdered medication is applied to the ulcer surface, most of the drug only remains on the mucosal surface through brief physical adsorption, quickly dissolving and being washed away by saliva and lost with swallowing, failing to form an effective drug reservoir at the ulcer site. This leads to an extremely short concentration window for the drug to exert its therapeutic effect, with local drug concentration rapidly declining to ineffective levels. To maintain basic efficacy, patients must administer the medication frequently (multiple times daily), resulting in poor medication adherence, significant drug waste, and difficulty in guaranteeing therapeutic efficacy. Summary of the Invention
[0005] Technical Problem to be Solved: To address the aforementioned technical problems, the present invention aims to provide a throat-specific inhaled powder and its preparation method. This inhaled powder comprises three-tiered sustained-release microspheres with a core-shell structure. The preparation method includes: S1. Loading Fritillaria cirrhosa, Typha pollen, and Angelica dahurica onto a modified hydroxyapatite-calcined borax composite microcore to form an inner long-acting sustained-release core; S2. Coating the inner microcore with an enzyme-responsive methacrylamide gelatin (Gelma) / poly(ε-caprolactone) (PCL) dual-network composite gel, and loading it with Phellodendron chinense, Coptis chinensis, human placenta extract, artificial bezoar, and natural borneol to form a middle medium-speed release drug layer; S3. Constructing an outer microneedle anchoring layer on the surface of the microspheres using chitosan quaternary ammonium salt infused with menthol through cryo-etching. The microspheres achieve physical anchoring and electrostatic adsorption through the outer microneedles, prolonging the retention time and releasing menthol for rapid pain relief upon contact with saliva; the middle gel responds to the degradation of the ulcer inflammatory microenvironment, releasing anti-inflammatory and antibacterial components; and the inner micronucleus slowly releases repair components, promoting mucosal healing. This achieves targeted retention and graded release of the drug, significantly improving drug utilization.
[0006] Technical solution: A throat-related inhaled powder, wherein the throat-related inhaled powder is a three-level sustained-release microsphere with a core-shell structure. The inner layer is a modified hydroxyapatite-calcined borax composite microcore loaded with Fritillaria cirrhosa, Typha pollen, and Angelica dahurica. The middle layer is an enzyme-responsive methacrylamide gelatin / poly(ε-caprolactone) dual-network composite gel loaded with Phellodendron chinense, Coptis chinensis, human placenta extract, artificial bezoar, and natural borneol. The outer layer is a micron-sized microneedle infused with menthol.
[0007] Furthermore, a method for preparing a throat-related nasal spray includes the following steps: S1. Hydroxyapatite and calcined borax are mixed and calcined in a high-temperature furnace at 800-1000℃ for 1-3 hours in air atmosphere. After cooling, an inorganic framework is obtained, which is then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane is added, and the mixture is reacted in a water bath at 60-80℃ for 4-8 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder is added. The mixture is shaken and mixed at 150-300 r / min for 20-40 minutes to obtain a modified inner layer composite microcore. S2. Natural borneol and poly(ε-caprolactone) are dissolved in dichloromethane, electrospun to form a composite nanofiber membrane, ground and dispersed in Gelma premix, and modified inner layer composite micronuclei are added. After stirring evenly, the membrane is crosslinked by 365nm ultraviolet light for 30-120s. After washing and drying, middle-inner layer composite microspheres are obtained. S3. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2-6% chitosan quaternary ammonium salt solution, add menthol, stir evenly, and obtain a film-forming solution; S4. Disperse the middle-inner layer composite microspheres in the film-forming solution, freeze them at -40~-80℃, and then freeze-dry them under vacuum to obtain the throat medicine powder.
[0008] Furthermore, in step S1, the mass ratio of hydroxyapatite to calcined borax is (3-5):1; the mass ratio of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder in the mixed powder is (1.5-2.5):(1.5-2.5):1; and the mass ratio of the solid to the mixed powder is (2-10):1.
[0009] Furthermore, in step S2, the mass-to-volume ratio of natural borneol, poly-ε-caprolactone, and dichloromethane is (0.1-0.2) g:1 g:10 mL; the electrospinning conditions are a voltage of 15-25 kV, a receiving distance of 10-20 cm, and a feed speed of 0.5-1.5 mL / h.
[0010] Furthermore, the preparation step of the Gelma premix in step S2 is as follows: Gelma, MMP-sensitive polypeptide cross-linking agent, salt-treated Phellodendron bark powder, Coptis chinensis powder, human placenta powder, artificial bezoar powder and photoinitiator are dissolved in pH 7.0 phosphate buffer at a mass ratio of 1g:(0.01-0.03)g:(0.1-0.15)g:(0.05-0.08)g:(0.05-0.08)g:(0.1-0.15)g:(0.02-0.05)g to obtain the Gelma premix.
[0011] Furthermore, the MMP-sensitive peptide crosslinking agent is PVGLIG, with the amino acid sequence Pro-Val-Gly-Leu-Ile-Gly; the photoinitiator is 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone Irgacure 2959.
[0012] Furthermore, in step S2, the mass-to-volume ratio of the composite nanofiber membrane, the Gelma premix, and the modified inner layer composite micronucleus is (0.1-0.5) g: 10 mL: (1-3) g.
[0013] Furthermore, in step S3, the amount of menthol added is 10-30% of the mass of chitosan quaternary ammonium salt.
[0014] Furthermore, in step S4, the mass-to-volume ratio of the middle-inner layer composite microspheres to the film-forming solution is (1-3) g: 10 mL.
[0015] The above-mentioned throat-clearing powder is used in the preparation of drugs for treating oral ulcers. Beneficial effects
[0016] This invention prepares a throat-related malnutrition powder, which is a three-level sustained-release microsphere comprising an inner composite microcore, a middle enzyme-responsive double-network gel coating layer, and an outer chitosan quaternary ammonium salt microneedle layer. The specific preparation method is as follows: (1) Pharmaceutical-grade hydroxyapatite powder is mixed with calcined borax and calcined at high temperature to obtain a hydroxyapatite-calcined borax inorganic framework. A silane coupling agent containing carboxyl groups is added, followed by the addition of Fritillaria cirrhosa powder, Typha pollen, and Angelica dahurica to obtain the inner composite microcore; (2) Natural borneol and PCL are dissolved together in an organic solvent, electrospun into a composite nanofiber membrane, and then immersed in a solution containing... In a solution of Gelma, MMP-sensitive polypeptide crosslinking agent and hydrophilic drug components, a double network composite gel is formed, and the inner layer composite micronucleus is dispersed in the premixed solution, so that the interpenetrating network gel is coated on the inner layer micronucleus; (3) Chitosan quaternary ammonium salt and menthol are mixed to obtain a film-forming solution, and then the middle-inner layer microspheres are dispersed in the film-forming solution and freeze-dried. Micron-sized conical microneedles are formed on the surface of the microspheres through the freeze etching effect. Menthol is molecularly dispersed and embedded in the polymer matrix of chitosan quaternary ammonium salt, becoming an inherent component of the microneedle structure, and finally a three-layer drug-loaded microsphere is obtained.
[0017] This invention applies the prepared throat-soothing powder to oral ulcer blowing medication, aiming to solve the technical problems of short retention time and low drug utilization rate of traditional blowing agents on oral ulcer surfaces. In specific applications, the three-layer core-shell structured microspheres can play the following roles: First, regarding the outer layer (rapid-release effective layer): ① Microneedle anchoring: The micron-sized microneedles on the surface can gently pierce the necrotic mucosa layer of the oral ulcer surface without mechanical stimulation or damage to normal mucosa, achieving physical anchoring; at the same time, the positive charge of chitosan quaternary ammonium salt and the negative charge of the damaged mucosa on the ulcer surface undergo electrostatic adsorption, forming a dual fixation of physical and electrostatic, which prolongs the carrier retention time and improves the problem of the inhaled drug being lost with saliva; ② Rapid analgesia: The microneedles swell rapidly upon contact with oral saliva, and the menthol in the hollow microcavity is released instantly, quickly acting on the nerve endings of the ulcer surface to exert a cooling and analgesic effect, immediately relieving the burning pain of the ulcer and improving the patient's discomfort when eating and speaking; Next, regarding the middle layer (medium-rate drug release layer): ① After the outer chitosan microneedles dissolve, the middle gel is exposed to the ulcer wound surface, where matrix metalloproteinases (MMP-2 / 9) are highly expressed at the ulcer inflammation site. ① It specifically recognizes and cleaves MMP-sensitive polypeptide cross-linking agents in the Gelma network, causing the hydrophilic Gelma network to degrade; ② The hydrophilic network rapidly releases anti-inflammatory and antibacterial components. Berberine from salted Phellodendron bark and Coptis chinensis broadly inhibits pathogenic bacteria such as Candida albicans and Staphylococcus aureus in the oral cavity, quickly controlling the inflammation at the core of the ulcer; Amino acids and polypeptides from human placenta regulate the local microenvironment of the oral cavity and assist in anti-inflammation; Bile acid components from artificial bezoar clear heat and detoxify, calm and relieve pain, alleviating the burning pain and redness of the ulcer; ③ Natural borneol encapsulated in PCL hydrophobic fibers is released, which can quickly penetrate deep into the ulcer mucosa, providing continuous analgesia and promoting the transdermal absorption of water-soluble components released in the hydrophilic area, enhancing the overall efficacy; ④ After the gel swells, it forms a thin, permeable hydrogel film, isolating the ulcer surface from the mechanical stimulation of food and saliva, and helping to protect the damaged mucosa; Finally, regarding the inner layer (long-lasting sustained-release layer): ① The carboxyl groups on the modified core surface can form amide bonds with the amino groups on the Gelma molecular chain, enhancing the interfacial bonding force and preventing interfacial peeling caused by swelling, friction, or degradation in the complex oral environment; ② The saponins in Fritillaria cirrhosa powder are slowly released, promoting the proliferation of mucosal epithelial cells on the oral ulcer surface, accelerating the growth of granulation tissue, and repairing damaged mucosa; ③ The flavonoids in Typha pollen continuously exert their blood-activating and anti-inflammatory effects, relieving congestion and microbleeds on the ulcer surface; ④ The coumarins and volatile oil components in Angelica dahurica are released in a long-lasting sustained manner, helping to inhibit oral pathogens and reducing inflammatory swelling and pain on the ulcer surface; ⑤ Calcined borax in the micronucleus is released with the degradation of the skeleton, continuously astringing the ulcer surface, reducing mucosal exudation, and preventing secondary irritation and infection of the ulcer surface by food residue and saliva. Attached Figure Description
[0018] Figure 1 A comparison of the clinical treatment effects of oral ulcers before treatment and 72 hours after using the throat-warming powder prepared in Example 8; Figure 2 A comparison of the clinical treatment effects of oral ulcers before treatment and 72 hours after using the throat-warming powder prepared in Example 7; Figure 3 A comparison of the clinical treatment effects of oral ulcers before treatment and 72 hours after using the throat-warming powder prepared in Example 3; Figure 4 A comparison of the clinical treatment effects of oral ulcers before treatment and 72 hours after using the throat-warming powder prepared in Comparative Example 5; Figure 5 A comparison of the clinical treatment effects of oral ulcers before treatment and 72 hours after using the throat-warming powder prepared in Comparative Example 4; Figure 6This is a comparison chart showing the clinical treatment effects of oral ulcers before treatment and 72 hours after using the throat-warming powder prepared in Comparative Example 3. Detailed Implementation
[0019] The present invention will be further described below with reference to the accompanying drawings and embodiments. The following embodiments are illustrative of the present invention, but the present invention is not limited to the following embodiments: Example 1
[0020] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 3:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 1.5:1.5:1 was added. The mass ratio of solid to mixed powder was 2:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.01g MMP-sensitive peptide crosslinking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.1 g:10 mL:1 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2% chitosan quaternary ammonium salt solution. Add 10% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 1g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat-related malnutrition powder. Example 2
[0021] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 5:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 1.5:1.5:1 was added, with a solid-to-mixed powder mass ratio of 2:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.01g MMP-sensitive peptide crosslinking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.1 g:10 mL:1 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2% chitosan quaternary ammonium salt solution. Add 10% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 1g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat-related malnutrition powder. Example 3
[0022] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.01g MMP-sensitive peptide crosslinking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.1 g:10 mL:1 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2% chitosan quaternary ammonium salt solution. Add 10% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 1g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat-related malnutrition powder. Example 4
[0023] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 10:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.01g MMP-sensitive peptide crosslinking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.1 g:10 mL:1 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2% chitosan quaternary ammonium salt solution. Add 10% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 1g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat-related malnutrition powder. Example 5
[0024] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.1 g:10 mL:1 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2% chitosan quaternary ammonium salt solution. Add 10% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 1g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat-related malnutrition powder. Example 6
[0025] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.5 g:10 mL:3 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2% chitosan quaternary ammonium salt solution. Add 10% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 1g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat-related malnutrition powder. Example 7
[0026] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.4 g:10 mL:2 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 6% chitosan quaternary ammonium salt solution. Add 10% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 1g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat-related malnutrition powder. Example 8
[0027] A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.4 g:10 mL:2 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 4% chitosan quaternary ammonium salt solution. Add 20% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 3g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat medicine powder. Comparative Example 1
[0028] The difference between this comparative example and Example 8 is that the carboxyl group of the core inorganic framework was not modified, as detailed below: A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained. A mixture of Fritillaria cirrhosa powder, Typha pollen powder and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 min to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.4 g:10 mL:2 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 4% chitosan quaternary ammonium salt solution. Add 20% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 3g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat medicine powder. Comparative Example 2
[0029] The difference between this comparative example and Example 8 is that no composite nanofiber membrane was added to the middle layer, as detailed below: A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Add the modified inner layer composite micronucleus to the Gelma premix solution at a mass-to-volume ratio of 10 mL: 2 g, stir until homogeneous, crosslink under 365 nm ultraviolet light for 80 s, wash and dry to obtain the middle-inner layer composite microspheres. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 4% chitosan quaternary ammonium salt solution. Add 20% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. Disperse the middle-inner layer composite microspheres in a film-forming solution at a mass-to-volume ratio of 3g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat medicine powder. Comparative Example 3
[0030] The difference between this comparative example and Example 8 is that the inner layer composite micronucleus is unmodified, as detailed below: A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S2. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix at a mass-to-volume ratio of 0.4 g:10 mL. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-layer composite microspheres were obtained. S3. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 4% chitosan quaternary ammonium salt solution. Add 20% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S4. Disperse the middle layer composite microspheres in the film-forming solution at a mass-to-volume ratio of 3g:10mL, freeze at -60℃, and then freeze-dry under vacuum to obtain the throat medicine powder. Comparative Example 4
[0031] The difference between this comparative example and Example 8 is the absence of a middle enzyme-responsive gel layer, as detailed below: A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S4. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 4% chitosan quaternary ammonium salt solution. Add 20% menthol by mass of chitosan quaternary ammonium salt and stir evenly to obtain a film-forming solution. S5. The modified inner layer composite micronucleus is dispersed in the film-forming solution at a mass-to-volume ratio of 3g:10mL. After being frozen at -60℃, it is then freeze-dried under vacuum to obtain the throat medicine powder. Comparative Example 5
[0032] The difference between this comparative example and Example 8 is that it lacks an outer microneedle anchoring layer, as detailed below: A method for preparing a throat-specific inhaled powder for infantile malnutrition includes the following steps: S1. Hydroxyapatite and calcined borax were mixed at a mass ratio of 4:1 and calcined in a high-temperature furnace at 800℃ for 2 hours in air atmosphere. After cooling, an inorganic framework was obtained, which was then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane was added, and the mixture was reacted in a water bath at 80℃ for 5 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder at a mass ratio of 2:2:1 was added. The mass ratio of solid to mixed powder was 6:1. The mixture was shaken and mixed at 200 r / min for 30 minutes to obtain the modified inner layer composite microcore. S2. Dissolve 1g Gelma, 0.03g MMP-sensitive peptide cross-linking agent, 0.1g salted Phellodendron bark powder, 0.08g Coptis chinensis powder, 0.05g human placenta powder, 0.1g artificial bezoar powder and 0.04g photoinitiator Irgacure 2959 in 10mL pH7.0 phosphate buffer to prepare Gelma premix solution; S3. Natural borneol and poly(ε-caprolactone) were dissolved in dichloromethane at a mass-to-volume ratio of 0.2 g:1 g:10 mL. The mixture was electrospun (voltage 20 kV, receiving distance 20 cm, feed speed 1.0 mL / h) to form a composite nanofiber membrane. After grinding, the membrane was dispersed in a Gelma premix and a modified inner layer composite micronucleus was added at a mass-to-volume ratio of 0.4 g:10 mL:2 g. The mixture was stirred until homogeneous and then crosslinked under 365 nm ultraviolet light for 80 s. After washing and drying, the middle-inner layer composite microspheres were obtained, which is the throat ailment powder. Performance testing:
[0033] (1) Particle size The particle size of the throat-related malnutrition powder prepared in Examples 1-8 and Comparative Examples 1-5 was determined using a laser particle size analyzer. The measurements were performed in three parallel trials, and the average value was taken.
[0034] Table 1. Particle sizes of the throat-related inhaled powders prepared in Examples 1-8 and Comparative Examples 1-5
[0035] As shown in Table 1, the average particle size of all embodiments is mainly distributed between 50-75 μm. This range is the ideal particle size for the aerosol, which avoids excessively large particles being inhaled into the lungs, while ensuring that the aerosol can pass smoothly through the nozzle of the powder sprayer and be evenly dispersed on the ulcer surface, thus prolonging the contact time of the drug at the target site.
[0036] Antibacterial activity Common oral pathogens (such as Staphylococcus aureus and Candida albicans) were selected. The culture medium for Staphylococcus aureus was tryptophan-soy agar (TSA), and the culture medium for Candida albicans was Sabouraud dextrose agar (SDA). The specific experimental steps are as follows: Preparation of bacterial suspension: The activated bacterial strain was diluted with sterile physiological saline to a concentration of approximately 1×10⁻⁶. 8 CFU / mL bacteria or 1×10 6 CFU / mL fungi; Plate preparation: Add the above bacterial suspension to TSA or SDA medium that has been sterilized and cooled to about 50°C at a volume ratio of 1%, mix gently, pour into plates to make uniform bacterial plates, and wait for them to solidify completely. Sample addition: Place 3 sterile Oxford cups at equal intervals on the surface of each plate. Weigh 10.0 ± 0.1 mg of the sample powder to be tested using a precision electronic balance, carefully fill the Oxford cups to the full, and gently compact them to ensure uniform, tight and seamless filling. Culture and observation: Place the plates upright in a 37℃ constant temperature incubator for culture (bacteria 24h, fungi 48h). Measurement: After the culture was completed, the diameter of each inhibition zone was accurately measured using vernier calipers (including the outer diameter of the Oxford cup, unit: mm). Each sample was tested in triplicate on the same plate, and the experiment was performed in parallel three times. The average value was taken.
[0037] Table 2 Diameter of inhibition zone
[0038] As shown in Table 2, the three-layer structure of the throat-clearing powder prepared in the examples exhibits good antibacterial effects. However, the throat-clearing powder prepared in the comparative examples with the absence of any layer will reduce the antibacterial activity to varying degrees by affecting drug release kinetics, interfacial stability, or component synergy.
[0039] (3) Practical application of oral ulcers Fifteen patients with simple oral ulcers were selected. The throat-spraying powder prepared according to the embodiments and comparative examples of this invention was applied to the affected area via a throat-spraying method, one spray each time, four times a day, for three days as one course of treatment. The patients' pain levels and ulcer healing time were recorded daily. Effective treatment was defined as the disappearance of pain and the healing of the ulcer; otherwise, it was ineffective. A commercially available watermelon frost spray was used as a control.
[0040] Table 3
[0041] As shown in Table 3, the throat-soothing powder prepared in this invention can quickly relieve pain and promote wound healing when treating oral ulcers. However, Comparative Example 1 lacks carboxyl groups on its core surface, resulting in a weak interfacial bond between the core and the gel layer due to physical encapsulation. This makes it prone to interlayer delamination in the complex oral environment, leading to premature leakage of the inner drug layer or disintegration of the carrier structure, thus failing to achieve long-term sustained release. Comparative Example 2 lacks the PCL / borneol hydrophobic network in its middle layer, consisting only of a gelma hydrophilic network. This alters the mechanical properties and degradation behavior of the entire gel layer, making it unable to achieve long-term sustained release. Effectively achieves domain-specific storage and synergistic release of hydrophilic / hydrophobic drugs; Comparative Example 3 lacks the inner layer composite micronucleus, which cannot achieve the three-level kinetics of "immediate release-intermediate release-long release", resulting in premature release of repair components and failure to continuously promote mucosal regeneration in the later stage; Comparative Example 4 lacks the middle layer enzyme-responsive gel layer, which directly coats the inner layer composite micronucleus on the outer layer, resulting in the loss of responsive drug release ability to the ulcer inflammatory microenvironment (high MMP expression); Comparative Example 5 lacks the outer layer microneedle anchoring layer, which makes the carrier unable to resist saliva erosion, shortening the mucosal retention time and thus slowing down the wound healing speed.
[0042] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any person skilled in the art can make many possible variations and modifications to the technical solutions of the present invention, or modify them into equivalent embodiments, without departing from the spirit and technical essence of the present invention. Therefore, any simple modifications, equivalent substitutions, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention, without departing from the content of the technical solutions of the present invention, shall still fall within the scope of protection of the present invention.
Claims
1. A throat-specific inhaled powder for infantile malnutrition, characterized in that: The throat-related nasal spray is a three-tiered sustained-release microsphere with a core-shell structure. The inner layer is a modified hydroxyapatite-calcined borax composite microcore loaded with Fritillaria cirrhosa, Typha pollen, and Angelica dahurica. The middle layer is an enzyme-responsive methacrylamide / poly(ε-caprolactone) dual-network composite gel loaded with Phellodendron chinense, Coptis chinensis, human placenta extract, artificial bezoar, and natural borneol. The outer layer is a micron-sized microneedle infused with menthol.
2. The preparation method of the throat-related inhaled powder according to claim 1, characterized in that, Includes the following steps: S1. Hydroxyapatite and calcined borax are mixed and calcined at 800-1000℃ for 1-3 hours. After cooling, an inorganic framework is obtained, which is then dispersed in anhydrous ethanol. An ethanol solution of 3-(carboxypropyl)triethoxysilane is added, and the mixture is reacted in a water bath at 60-80℃ for 4-8 hours. After centrifugation, solid collection, washing, and drying, a mixture of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder is added and the mixture is shaken to obtain a modified inner layer composite microcore. S2. Natural borneol and poly(ε-caprolactone) are dissolved in dichloromethane, electrospun to form a composite nanofiber membrane, ground and dispersed in Gelma premix, and modified inner layer composite micronuclei are added. After stirring evenly, the membrane is crosslinked by ultraviolet light for 30-120 seconds, washed and dried to obtain middle-inner layer composite microspheres. S3. Dissolve hydroxypropyltrimethylammonium chloride chitosan in 1% acetic acid solution to prepare a 2-6% chitosan quaternary ammonium salt solution, add menthol, stir evenly, and obtain a film-forming solution; S4. Disperse the middle-inner layer composite microspheres in a film-forming solution, freeze them at low temperature, and then freeze-dry them under vacuum to obtain the throat medicine powder.
3. The preparation method of the throat-related inhaled powder according to claim 2, characterized in that, In step S1, the mass ratio of hydroxyapatite to calcined borax is (3-5):1; the mass ratio of Fritillaria cirrhosa powder, Typha pollen powder, and Angelica dahurica powder in the mixed powder is (1.5-2.5):(1.5-2.5):1; and the mass ratio of the solid to the mixed powder is (2-10):
1.
4. The preparation method of the throat-related inhaled powder according to claim 2, characterized in that, In step S2, the mass-to-volume ratio of natural borneol, poly-ε-caprolactone, and dichloromethane is (0.1-0.2) g:1 g:10 mL; the electrospinning conditions are a voltage of 15-25 kV, a receiving distance of 10-20 cm, and a feed speed of 0.5-1.5 mL / h.
5. The preparation method of a throat-related inhaled powder according to claim 2, characterized in that, The preparation step of the Gelma premix in step S2 is as follows: Gelma, MMP-sensitive polypeptide cross-linking agent, salt-treated Phellodendron bark powder, Coptis chinensis powder, human placenta powder, artificial bezoar powder and photoinitiator are dissolved in pH 7.0 phosphate buffer at a mass ratio of 1g:(0.01-0.03)g:(0.1-0.15)g:(0.05-0.08)g:(0.05-0.08)g:(0.1-0.15)g:(0.02-0.05)g to obtain the Gelma premix.
6. The preparation method of the throat-related inhaled powder according to claim 5, characterized in that, The MMP-sensitive peptide crosslinking agent is PVGLIG, with the amino acid sequence Pro-Val-Gly-Leu-Ile-Gly; the photoinitiator is Irgacure2959.
7. The preparation method of a throat-related inhaled powder according to claim 2, characterized in that, In step S2, the mass-to-volume ratio of the composite nanofiber membrane, Gelma premix, and modified inner layer composite micronucleus is (0.1-0.5) g: 10 mL: (1-3) g.
8. The preparation method of a throat-related inhaled powder according to claim 2, characterized in that, In step S3, the amount of menthol added is 10-30% of the mass of chitosan quaternary ammonium salt.
9. The preparation method of a throat-related inhaled powder according to claim 2, characterized in that, In step S4, the mass-to-volume ratio of the middle-inner layer composite microspheres to the film-forming solution is (1-3) g: 10 mL.
10. The use of the throat-clearing powder according to claim 1 in the preparation of a medicine for treating oral ulcers.