A nasal disease external traditional Chinese medicine composition and extract, and a preparation method and application thereof

Abstract

The present application relates to the field of traditional Chinese medicine, and discloses a kind of external use traditional Chinese medicine composition and extract for nasal diseases and its preparation method and application.The composition is composed of Xanthium sibiricum, Eupatorium Fortunei, Pogostemonis Herba, wild chrysanthemum, perilla stem, Polygonatum, and Trollius chinensis, and the preparation process includes subsection decoction, clarification pretreatment, subsection gradient MVR concentration and constant-temperature curing process.The finished product of the present application has high retention rate of heat-sensitive active substances;the extract has a foam height of only 5-8 mm, and the defoaming is fast;the minimum fouling of MVR concentration pipe wall is 11.1 g, and the evaporation efficiency can reach 46.0 kg / h;there is no turbidity and precipitation after sealed storage for 30 days, and the stability is excellent.The ciliary oscillation time of medicinal liquid is 308-341 min, and the mucous membrane irritation is low;the total polyphenol release rate is only 16.2% in 1 h, there is no obvious burst release, and the release reaches 94.80% in 10 h, so the nasal cavity can be acted for a long time.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, and more specifically, to a topical traditional Chinese medicine composition and extract for nasal diseases, its preparation method, and its application. Background Technology

[0002] Traditional Chinese medicine for nasal inflammation often uses a combination of Xanthium sibiricum, Centipeda minima, and Pogostemon cablin, which has a significant effect on clearing the nasal passages. However, these herbs are rich in water-soluble triterpenoid saponins, which easily generate stable foam during concentration. This can lead to mist entrainment, loss of active ingredients, and even damage to the MVR compressor during production. To address the high energy consumption of traditional vacuum concentration, existing technologies have introduced energy-saving MVR concentration processes. For example, CN112494536A discloses a method for preparing nasal drug extracts, using Xanthium sibiricum, Centipeda minima, Pogostemon cablin, Ephedra sinica, and Chrysanthemum indicum as raw materials. The extract is decocted twice at high temperatures, and the filtrate is directly fed into a single constant-condition MVR for concentration.

[0003] While this approach relies on MVR to reduce energy consumption, it has significant flaws. The formulation lacks medicinal materials capable of endogenously suppressing foam and repairing nasal mucosal damage, relying solely on the single component of buddleja officinalis for quality control. It fails to address issues such as foaming of the decoction and the easy oxidation of polyphenols by limiting the quality of raw materials. During the extraction stage, all medicinal materials are simultaneously boiled at high temperatures. Prolonged high temperatures cause a large amount of aromatic and heat-sensitive medicinal components to volatilize and polyphenols to oxidize and degrade. After boiling, only the dregs are simply filtered out, leaving all free saponins and large molecular colloids in the decoction to enter the concentration system. The equipment's simple defoaming structure alone is insufficient to prevent foam leakage.

[0004] This MVR operates under constant vacuum and temperature throughout the process. As concentration progresses, the solid content and viscosity of the material continuously increase, leading to a sustained increase in heat exchange resistance and easy fouling on the heat exchange tube walls, resulting in a continuous decline in evaporation efficiency. The material's circulation time within the equipment relies entirely on the feed flow rate for rough adjustment, making it difficult to stably control the degree of heating, ultimately causing significant fluctuations in the effective components of the final extract. Conventional defoaming methods in the industry often involve the addition of chemical defoamers, which can easily irritate the delicate nasal mucosa. Existing technologies struggle to simultaneously meet the multiple requirements of active ingredient retention, production foam and scale prevention, storage stability, nasal mucosa safety, and long-lasting sustained release. Summary of the Invention

[0005] To overcome the shortcomings of the prior art mentioned above, which makes it difficult to simultaneously meet the multiple requirements of retaining active ingredients, inhibiting foaming and scale formation during production, ensuring storage stability, ensuring nasal mucosa safety, and providing long-lasting sustained release, this invention provides a topical Chinese medicine composition for nasal diseases. Another objective of this application is to provide an application of a topical traditional Chinese medicine composition for nasal diseases; Another objective of this application is to provide an extract of a topical traditional Chinese medicine composition for nasal diseases; Another objective of this application is to provide a method for preparing an extract of a topical traditional Chinese medicine composition for nasal diseases.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows: A topical Chinese medicine composition for nasal diseases, comprising the following components in parts by weight: 260-380 parts of Xanthium sibiricum, 260-380 parts of Centipeda minima, 220-380 parts of Pogostemon cablin, 120-240 parts of Chrysanthemum indicum, 100-170 parts of Perilla frutescens stem, 70-150 parts of Polygonatum odoratum, and 55-110 parts of Trollius chinensis.

[0007] Furthermore, the total water-soluble polysaccharide content in the Polygonatum odoratum is ≥9% by mass; and the total polyphenol content in the Nasturtium floridum is ≥2.2% by mass.

[0008] Furthermore, the total saponin content of the *Centipeda minima* is above 2%.

[0009] Preferably, the water-soluble pectin impurities in *Centipeda minima* are ≤3%; the content of berberine alcohol in *Pogostemon cablin* is ≥0.20%; the total flavonoid content in *Chrysanthemum indicum* is ≥4.5%; and the content of water-soluble pectin impurities in *Perilla frutescens* stem is ≤2.5%.

[0010] Polysaccharides from Polygonatum odoratum can complex with free saponins in the drug solution, reducing the surface activity of the system and inhibiting foaming during subsequent solution preparation and filling; at the same time, they encapsulate polyphenols for antioxidant and color protection. Polyphenols from Napier lotus also possess anti-inflammatory activity and synergistically stabilize the ointment with polysaccharides, reducing oxidation and discoloration during storage. These two indicators ensure the system's endogenous stability and achieve the desired foam suppression and color protection effects. Excessive saponin content causes significant foaming during concentration and formulation stages, requiring a balance between efficacy and production stability. Excessive colloidal impurities significantly increase the viscosity of the drug solution, leading to scaling on the concentration heat exchange tubes, membrane filtration blockage, and increased ointment wall adhesion loss.

[0011] An application of the aforementioned topical traditional Chinese medicine composition for nasal diseases, used to prepare drugs for rhinitis, nasal mucosal inflammation, and nasal dryness and damage.

[0012] In the medicinal solution, Polygonatum odoratum polysaccharides form a hydrogen-bonded complex network colloidal structure with saponins and polyphenolic active substances, naturally constructing an endogenous sustained-release delivery system. When applied to the nasal mucosa, the polysaccharide colloid can adhere to the nasal epithelium to form a moisturizing protective film, reducing drug loss. In the weakly acidic microenvironment of the nasal cavity, the complex bonds slowly dissociate, and the nasal-clearing saponins and anti-inflammatory flavonoid polyphenols encapsulated within the polysaccharide network are gradually and steadily released, achieving a local long-term sustained-release effect, prolonging the duration of efficacy of a single dose, avoiding the rapid loss of free active ingredients that could cause short-term efficacy and local irritation, while synergistically enhancing the mucosal repair effect.

[0013] An extract of a topical traditional Chinese medicine composition for nasal diseases, prepared from the topical traditional Chinese medicine composition for nasal diseases.

[0014] A method for preparing an extract of the aforementioned topical traditional Chinese medicine composition for nasal diseases includes the following steps: S1. Segmented and sealed decoction: First, add water to the cocklebur, centipeda minima and polygonatum and decoct; then add patchouli, wild chrysanthemum, perilla stem and golden lotus and decoct together, and collect the decoction. S2. Clarification Pretreatment: After cooling the decoction, adjust the pH, add chitosan and stir to flocculate, then centrifuge to remove colloids, free saponins and colloidal aggregates to obtain a clarified extract and keep it warm for storage. S3. Segmented gradient MVR concentration: The clarified extract after heat preservation is concentrated by segmented gradient variable parameter MVR evaporation, and the heating residence time is controlled. After the concentrate is matured, the extract of the topical Chinese medicine composition for nasal diseases is obtained.

[0015] Furthermore, when decocting S1, the mass of water added should be 9 to 11 times the total mass of the topical Chinese medicine composition for nasal diseases; decoct at 90 to 98°C for 1.5 to 2 hours first, and then decoct again at 85 to 92°C for 20 to 35 minutes.

[0016] Preferably, the mixture is first simmered at 92-96℃ for 1.5-2 hours, and then simmered again at 86-90℃ for 20-35 minutes.

[0017] Preferably, the mixture is first simmered at 95°C for 2 hours, and then simmered again at 90°C for 30 minutes.

[0018] First, the densely cell-walled Xanthium sibiricum, Centipeda minima, and Polygonatum odoratum are extracted at a relatively high temperature for a long time to ensure the full dissolution of saponins and water-soluble polysaccharides from Polygonatum odoratum. Then, heat-sensitive medicinal materials containing volatile oils and polyphenols, such as Patchouli and Trollius chinensis, are added and the extraction temperature is lowered to significantly reduce the loss of volatile oils and the high-temperature oxidation loss of polyphenols. The segmented extraction reduces the production of excessive free saponins from high-temperature boiling, alleviating the problem of excessive foaming in the concentration stage from the source. The viscosity of the medicinal solution is also lower, making it suitable for the subsequent ceramic membrane impurity removal process.

[0019] Furthermore, the amount of chitosan added in S2 is 0.03%~0.06% of the decoction mass, and the centrifugation speed is 8000~10000 r / min.

[0020] Preferably, the decoction is cooled to 30-40°C and the pH of the system is adjusted to 5.0-6.0.

[0021] The chitosan flocculation system of the present invention effectively removes disordered colloids, stray nanocolloids and other interfering impurities in the drug solution. It can not only eliminate the problem of impurities occupying binding sites and interfering with the orderly assembly of supramolecular structures, but also remove organic colloids that are easily deposited when heated in advance, and reduce the formation of organic scale on the heat exchange tube wall during the subsequent MVR concentration stage.

[0022] Furthermore, S3 is divided into two stages of gradient concentration: the first stage temperature is 70~80℃, and the second stage temperature is 65~75℃, with the first stage concentration temperature being higher than the second stage concentration temperature; the heating residence time does not exceed 20 min.

[0023] Preferably, the temperature of the first stage is 77°C and the temperature of the second stage is 70°C; the heating time does not exceed 16~18 min.

[0024] The initial stage uses high vacuum and low temperature to treat the diluted extract, suppressing excessive foam generation and protecting heat-sensitive components such as polyphenols and volatile oils from high-temperature degradation. The subsequent stage appropriately reduces the vacuum and increases the evaporation temperature to suit the high-viscosity liquid in the later stage of concentration, ensuring efficient water evaporation and reducing the loss of thick paste adhering to the wall. The total heating time of the materials is strictly limited to shorten the high-temperature contact time of active ingredients. Combined with the intermediate density determination node, the timing of shutdown is precisely controlled to prevent the liquid from being over-concentrated and coking, and to smoothly connect to the subsequent ripening and stabilization process.

[0025] Furthermore, when the relative density of the concentrate at 50°C is 1.06~1.10, it is transferred to a sealed, heat-insulated maturation tank and allowed to stand at 58~62°C for 40~60 minutes to mature.

[0026] Preferably, the mixture is transferred to a sealed, insulated curing tank and allowed to stand at 60°C for 50 minutes to mature.

[0027] Maturation promotes the full complexation of residual trace amounts of free saponins with Polygonatum polysaccharides in the system, reducing the foaming ability of the paste itself and avoiding foaming during subsequent formulation stirring and filling processes that could lead to dosage deviations; the polysaccharide component can encapsulate polyphenols to isolate them from oxygen, inhibiting the oxidation and discoloration of the extract during long-term storage; at the same time, it optimizes the rheological properties of the paste and reduces material loss due to wall adhesion.

[0028] Preferably, when the material is aged to a relative density of 1.12~1.15 at 60°C, the extract of the topical Chinese medicine composition for nasal diseases is obtained.

[0029] Preferably, the extract of the traditional Chinese medicine composition can be processed into any dosage form for external use in the nasal cavity, such as nasal drops, nasal sprays, nasal gels, ointments, or films, according to conventional pharmaceutical processes.

[0030] This invention innovatively introduces Polygonatum odoratum, whose water-soluble polysaccharide molecular chains form a three-dimensional colloidal network framework with a large number of hydroxyl groups. During the sealed curing process, the polysaccharide hydroxyl groups can form intermolecular hydrogen bonds with the phenolic hydroxyl groups of Trollius chinensis polyphenols and the hydrophilic sugar groups of triterpenoid saponins in Xanthium sibiricum and Centipeda minima, respectively. At the same time, the aromatic rings of polyphenols and the carbon chains of polysaccharides generate π-π hydrophobic stacking. Polyphenols act as cross-linking nodes, saponins fill the network pores, and polysaccharide chains intertwine with each other. The three are assembled stepwise through multiple non-covalent bonds to construct a three-dimensional, interconnected polysaccharide-polyphenol-saponin reversible supramolecular network colloid.

[0031] During production, the polysaccharide complexes free saponins, reducing the surface activity of the system and endogenously inhibiting foaming. At the same time, it encapsulates polyphenols and volatile oils to isolate them from high temperatures and oxygen, reducing the oxidative degradation of active ingredients. During the formulation storage stage, the network structure blocks oxygen and delays browning and precipitation. When acting on the nasal mucosa, the colloid can adhere to the epithelium to form a moisturizing buffer protective film. The weakly acidic environment of the nasal cavity will slowly break the complexed hydrogen bonds, and the network will gradually expand, allowing the internal active components to be released steadily, avoiding sudden release and mucosal irritation.

[0032] Compared with the prior art, the beneficial effects of the technical solution of the present invention are: 1. Excellent retention of active ingredients: The content of mongholic acid in the finished product is 1.25~1.54 mg / g; patchouli 158~213 μg / g; total polyphenols 5.05~6.61 mg / g; effectively retaining flavonoids, volatile oils, and heat-sensitive active substances such as polyphenols. 2. It has its own endogenous defoaming properties. After the extract is diluted, the foam height is only 5~8 mm and the foam dissipation time is 2.6~4.5 minutes. It is not easy to generate a lot of foam during the production concentration and filling stages, and there is no need to add chemical defoamers. 3. It is suitable for industrial concentration of MVR, with a minimum scale buildup of only 11.1 g on the heat exchange tube wall and a maximum evaporation rate of 46.0 kg / h per unit time. It has high heat exchange efficiency and is less prone to problems such as pipe blockage and material coking on the wall. 4. Excellent storage stability: The extract remains a light yellow, clear liquid after 30 days of sealed storage at room temperature, protected from light, without turbidity, precipitation, or obvious browning. 5. It has excellent safety for nasal mucosa. The extract has extremely low irritation to nasal cilia. The normal cilia movement time can reach 308~341 minutes, which can protect the physiological function of nasal cilia. 6. It has a long-lasting nasal release effect. Using total polyphenols as an indicator, the cumulative release rate is only 16.20% in 1 hour. There is no initial drug burst release. The release curve is flat and gradual. The cumulative release rate reaches 94.80% in 10 hours. It can achieve stable and continuous nasal administration for up to 10 hours, increase the duration of action of a single dose, and reduce local drug irritation. Attached Figure Description

[0033] Figure 1 The cumulative release rate of polyphenols at different sampling times. Detailed Implementation

[0034] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0035] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0036] Raw materials meeting the following standards were selected: Polygonatum odoratum (water-soluble total polysaccharides ≥9%); Nasturtium floridum (total polyphenols ≥2.2%); Centipeda minima (total saponins ≥2%, water-soluble colloidal impurities ≤3%); Patchouli (purple alcohol content ≥0.20%); Chrysanthemum indicum (total flavonoids ≥4.5%); Perilla frutescens (water-soluble impurities colloidal content ≤2.5%). Chitosan had a degree of deacetylation ≥85% and a weight-average molecular weight of 150 kDa~400 kDa.

[0037] Example 1 Take the following ingredients by weight: 320 parts of Xanthium sibiricum, 320 parts of Centipeda minima, 300 parts of Pogostemon cablin, 180 parts of Chrysanthemum indicum, 135 parts of Perilla frutescens stem, 110 parts of Polygonatum odoratum, and 80 parts of Nasturtium lappa. Take each herb according to the ratio, add purified water 10 times the total weight of the herbs, first add Xanthium sibiricum, Centipeda minima, and Polygonatum odoratum, and soak at a constant temperature of 95℃ for 2 hours; then add Pogostemon cablin, Chrysanthemum indicum, Perilla frutescens stem, and Nasturtium floridum, adjust the temperature to 90℃ and continue soaking for 30 minutes, and collect all the decoction.

[0038] The decoction was cooled to 35°C, and the pH of the system was adjusted to 5.0-6.0. Chitosan (0.05% by weight of the decoction) was added, and the mixture was centrifuged at 8500 r / min to obtain a clear and stable extract filtrate.

[0039] The clarified filtrate was then concentrated using a two-stage gradient MVR evaporation. The first stage was controlled at 77°C, and the second stage at 70°C. The total heating time of the material was strictly controlled to be 16 minutes throughout the process to maximize the retention of heat-sensitive active ingredients. Samples were taken for testing, and the MVR evaporation operation was stopped when the relative density of the sample at 50°C reached 1.06~1.10.

[0040] The medicinal liquid, having reached an intermediate density, was transferred to a sealed maturation tank, where it was allowed to cool naturally at a gradient and maintained at a constant temperature of 60°C for 50 minutes. After maturation, a sample was taken, and the relative density of the medicinal liquid was measured at 60°C to be 1.06~1.10, thus obtaining the extract of the topical Chinese medicine composition for nasal diseases.

[0041] Example 2 The technical solution is similar to that of Embodiment 1, except that: Take the following ingredients by weight: 260 parts of Xanthium sibiricum, 260 parts of Centipeda minima, 220 parts of Pogostemon cablin, 120 parts of Chrysanthemum indicum, 100 parts of Perilla frutescens stem, 70 parts of Polygonatum odoratum, and 55 parts of Trollius chinensis. Add 9 times the total weight of the herbs to purified water. First, add Xanthium sibiricum, Centipeda minima, and Polygonatum odoratum and extract at a constant temperature of 90°C for 1.5 hours. Then add the remaining herbs and adjust the temperature to 85°C and soak for a total of 20 minutes. Collect all the decoction.

[0042] The decoction was cooled to 30℃, and the pH of the system was adjusted to 5.0~6.0. Chitosan (0.03% by weight of the decoction) was added, and the mixture was centrifuged at 8000 r / min to obtain a clear and stable extract filtrate.

[0043] The filtrate was concentrated using a two-stage gradient MVR process: the first stage evaporation temperature was 70℃; the second stage evaporation temperature was 65℃, and the total residence time of the material under heat was 14 min.

[0044] The concentrate was transferred to a sealed, insulated maturation tank and kept at a constant temperature of 58°C for 40 minutes to mature. The resulting material was then discharged to obtain an extract of a topical Chinese medicine composition for nasal diseases.

[0045] Example 3 The technical solution is similar to that of Embodiment 1, except that: Take the following ingredients by weight: 380 parts of Xanthium sibiricum, 380 parts of Centipeda minima, 380 parts of Pogostemon cablin, 240 parts of Chrysanthemum indicum, 170 parts of Perilla frutescens stem, 150 parts of Polygonatum odoratum, and 110 parts of Trollius chinensis. Add 11 times the total weight of the herbs to purified water. First, add Xanthium sibiricum, Centipeda minima, and Polygonatum odoratum and extract at a constant temperature of 98°C for 2 hours. Then add the remaining herbs and adjust the temperature to 92°C and soak for a total of 35 minutes. Collect all the decoction.

[0046] The decoction was cooled to 40℃, and the pH of the system was adjusted to 5.0~6.0. Chitosan (0.06% by weight of the decoction) was added, and the mixture was centrifuged at 10000 r / min to obtain a clear and stable extract filtrate.

[0047] Two-stage gradient MVR concentration of filtrate: first stage evaporation temperature 80℃; second stage evaporation temperature 75℃, total heat residence time of material 20 min.

[0048] The concentrate was transferred to a sealed, insulated maturation tank and kept at a constant temperature of 62°C for 60 minutes. The resulting material was then discharged to obtain an extract of a topical Chinese medicine composition for nasal diseases.

[0049] Comparative Example 1 The technical solution is similar to that of Example 1, except that: all medicinal materials are added together at once, and purified water is added at a total weight of 10 times the total weight of the medicinal materials. The mixture is decocted at a constant temperature of 90°C for 2 hours. After decoction, the residue is removed by coarse filtration with gauze to obtain a crude extract. The crude extract is sent to a dual-effect MVR system, where the system material is preheated to 78°C with 135°C live steam and the preheating valve is closed. The system is then concentrated using a dual-effect continuous circulation mode (first-effect vacuum degree -50 kPa, evaporation temperature 82~85°C, second-effect vacuum degree -80 kPa, evaporation temperature 63~66°C). The product is then directly discharged after continuous concentration to the final density of the finished product, without the need for sealed constant temperature static ripening treatment.

[0050] Comparative Example 2 The technical solution is similar to that of Example 1, except that all medicinal materials are put into water and decocted together at 95°C for 2 hours.

[0051] Comparative Example 3 The technical solution is similar to that of Example 1, except that after decoction, only ordinary gauze is used for coarse filtration to remove the dregs, without going through the chitosan flocculation and impurity removal process, and directly enters the MVR concentration process.

[0052] Comparative Example 4 The technical solution is similar to that of Example 1, except that: after the MVR is concentrated to a relative density of 1.06~1.10 at 50℃, it is not placed in a maturation tank for constant temperature standing, but is directly concentrated to a relative density of 1.12~1.15 at 60℃ before being discharged.

[0053] Comparative Example 5 The technical solution is similar to that of Example 1, except that the duration of the material being heated throughout the process is controlled to be 25 minutes.

[0054] Comparative Example 6 The technical solution is similar to that of Example 1, except that it does not use two-stage gradient vacuum and gradient temperature concentration, and maintains a constant evaporation temperature of 82°C throughout the concentration process.

[0055] Comparative Example 7 The technical solution is similar to that of Example 1, except that the curing temperature is set to 55°C and the curing time is 30 min.

[0056] Comparative Example 8 The technical solution is similar to that of Example 1, except that chitosan is not added and the extract is obtained directly after centrifugation.

[0057] Comparative Example 9 The technical solution is similar to that of Example 1, except that the decoction is cooled to 20-25°C, the pH is adjusted to 4.5, and then chitosan is added.

[0058] Comparative Example 10 The technical solution is similar to that of Example 1, except that: 68.7 parts of patchouli, 85.7 parts of cocklebur, 85.7 parts of centipeda minima, 43 parts of ephedra and 43 parts of wild chrysanthemum are weighed according to the following weight parts.

[0059] Comparative Example 11 The technical solution is similar to that of Example 1, except that Solomon's seal is not added.

[0060] Comparative Example 12 The technical solution is similar to that of Example 1, except that no golden lotus flowers are added.

[0061] Comparative Example 13 The technical solution is similar to that of Example 1, except that the weight of Polygonatum odoratum is adjusted to 60 parts.

[0062] Comparative Example 14 The technical solution is similar to that of Example 1, except that the weight of the golden lotus is adjusted to 120 parts.

[0063] Detection methods 1. Detection of the content of thermosensitive active ingredients (1) Detection of Buddleja glycoside content in concentrated solution Weigh an appropriate amount of buddlejawine reference standard, dissolve it in methanol, and prepare a reference solution with a concentration of 30 μg / mL. Accurately weigh 0.9 g of the concentrated sample and place it in a 50 mL volumetric flask. Add 40 mL of methanol, sonicate for 15 min, cool, add methanol to the mark, shake well, filter, and collect the filtrate to obtain the test solution. Inject 10 μL each of the reference solution and the test solution into the liquid chromatograph to determine the concentration of buddlejawine.

[0064] Liquid chromatography conditions: Octadecylsilane-bonded silica gel was used as the stationary phase; methanol-4% glacial acetic acid solution (47.5:52.5) ​​was used as the mobile phase; the flow rate was 0.8 mL / min; the detection wavelength was 334 nm; and the injection volume was 20 μL.

[0065] (2) Detection of the content of baicalein in the concentrate Weigh an appropriate amount of baicalein reference standard, dissolve it in anhydrous ethanol and dilute to volume to prepare a 40 μg / mL reference standard solution. Weigh 1.0 g of each group's concentrated solution, add 25 mL of anhydrous ethanol, extract by sonication for 20 min, cool to room temperature, dilute to volume, filter through a microporous membrane, and collect the filtrate for analysis.

[0066] Gas chromatography conditions: capillary DB-5 column; temperature program: initial 120℃, hold for 3 min, increase to 220℃ at 5℃ / min, hold for 8 min; carrier gas nitrogen, flow rate 1.0 mL / min; FID detector temperature 250℃; split injection, injection volume 1 μL.

[0067] (3) Detection of total polyphenol content in concentrate Weigh gallic acid reference standard dried to constant weight and dissolve in water to prepare a 50 μg / mL standard working solution. Weigh 0.5 g of each group's concentrated solution, add water to a final volume of 25 mL, shake well, and dilute to a suitable concentration for later use. Take 2 mL of the diluted test solution, add 1 mL of Folin-Ciocalteu reagent, shake well, let stand for 5 min, then add 2 mL of 10% sodium carbonate solution, and dilute to a final volume of 10 mL with pure water. Let stand in the dark for 30 min. Zero the instrument with a blank reagent and measure the absorbance at a wavelength of 765 nm. Calculate the total polyphenol content (calculated as gallic acid) using the standard curve.

[0068] 2. Foaming properties of the extract Dilute each extract with pure water to 10% solids, take 150 mL and place it in a 250 mL graduated measuring cylinder, and let it stand at a constant temperature of 25℃ for 30 min to equilibrate. Stir at 12000 r / min for 3 min in a high-speed homogenizer, and record the total height of foam immediately after stopping stirring; start timing until no foam is visible to the naked eye in the measuring cylinder, and record the total dissipation time.

[0069] 3. MVR Concentration Scaling and Concentration Efficiency Testing The solids content of the filtrate in each group was uniformly adjusted to 5%, with a single feed rate of 50 L. The corresponding process was operated according to the set temperature and total heating time until 2 kg of solids were produced. The total time consumed throughout the process was recorded, and the water evaporation rate per unit time (kg / h) was calculated. After concentration, the heat exchange tubes were removed, and the soluble materials on the tube walls were rinsed with pure water. The residue was dried at 105℃ to constant weight, and the mass of the dried scale was weighed.

[0070] 4. Storage stability test The extract samples were treated with 0.01% benzalkonium chloride for preservation, sealed and protected from light at room temperature for 30 days, and graded by color (Grade 1: light yellow, no turbidity and no precipitation; Grade 2: dark yellow, slightly turbid; Grade 3: brownish-brown, obvious precipitation).

[0071] 5. Comprehensive performance evaluation of nasal mucosa (1) Cilia safety Fresh palatal mucosa tissue from a live toad was spread flat on a glass slide, 0.1 mL of the sample was added, and the duration of normal ciliary movement was recorded under a microscope.

[0072] (2) In vitro simulated nasal mucosa sustained-release detection A pH 6.8 phosphate buffer solution was prepared to simulate the physiological fluid environment of the nasal cavity as the release and receiving solution. 2 g of each extract was weighed, placed into a dialysis bag with a molecular weight cutoff of 8000–14000 Da, and sealed. The dialysis bag was completely immersed in 200 mL of the receiving solution at a constant temperature of 32°C with low-speed stirring. 5 mL samples were taken at 1 h, 2 h, 4 h, 6 h, and 8 h, and an equal volume of blank buffer was added simultaneously.

[0073] First, the total polyphenol concentration in each sample solution was determined using the Folin-gallic acid standard curve method, and the true polyphenol concentration in the medium was calculated. Since an equal volume of blank buffer was added after each sampling, the release amount at each time point needed to be corrected by volume. The total cumulative release amount was obtained by summing the mass of polyphenols taken away in each sampling. The cumulative release percentage of active ingredients at each time point was calculated using the initial total polyphenol mass in the dialysis bag as the denominator.

[0074] Analysis and Explanation 1. Content of active ingredients in the extract As shown in Table 1, the contents of mongholic acid in the examples were 1.25~1.54 mg / g, patchouli alcohol 158~213 μg / g, and total polyphenols 5.05~6.61 mg / g.

[0075] Table 1 Content of active ingredients

[0076] In Comparative Example 1, under continuous high-temperature treatment, the content of buddleja glycoside was only 1.10 mg / g, and the content of apricot kernel alcohol and total polyphenols decreased by 27.95% and 19.07% respectively compared to Example 1. The prolonged high-temperature processing resulted in significant loss of these three heat-sensitive components. In Comparative Example 2, patchouli, golden lotus, and wild chrysanthemum were not processed with a low-temperature follow-up step and were decocted at high temperatures for an extended period. The volatilization loss of apricot kernel alcohol was the most significant, and the content of these three active ingredients was the lowest among all the complete seven-ingredient formulas. Comparative Examples 5 and 6 exhibited defects such as excessive MVR heating time and lack of two-stage gradient low-temperature protection. The medicinal solution was kept in a relatively high-temperature environment throughout the process, resulting in significantly higher oxidation of flavonoids and polyphenols and volatilization of volatile oils compared to the gradient temperature control process of this invention, leading to a significant decrease in the retention rate of active ingredients.

[0077] Comparative Example 8: High-speed centrifugation alone could not remove the colloidal and free saponin micro-colloidal aggregates in the drug solution; colloidal impurities continued to adsorb active components, resulting in a significant decrease in the content of mongholic acid and baicalein, and a particularly prominent loss of total polyphenols. Comparative Example 9: Chitosan's charge neutralization and bridging flocculation capabilities decreased, resulting in smaller flocs and a poorer centrifugal impurity removal effect.

[0078] The formulations of Comparative Examples 12 and 10 did not contain golden lotus, and the system lacked characteristic polyphenol components, with total polyphenol detection values ​​of only 0.62~0.64 mg / g; at the same time, the synergistic antioxidant system of polyphenols and Solomon's seal polysaccharides was missing, and the degradation rate of buddleja glycosides and baicaleol increased during the heating process, and their contents decreased simultaneously.

[0079] Comparative Examples 11 and 13 lacked Polygonatum odoratum or had a reduced proportion of Polygonatum odoratum, resulting in a lack of sufficient water-soluble polysaccharides to form a complex protective structure. This made it impossible to isolate the active molecules from the damage caused by heat and oxygen, and the retention rates of mongholic acid, baicalein, and total polyphenols were significantly lower than in the examples.

[0080] In Comparative Example 14, the addition of nasturtium resulted in an acidic environment due to excessive polyphenols. Under high temperature, this catalyzed the hydrolysis of buddleja glycosides, while the polyphenols themselves underwent oxidative polymerization, leading to a simultaneous decrease in both indicators.

[0081] 2. Foaming properties of the extract As shown in Table 2, the total foam height in the embodiments of the present invention is only 5~8 mm, and the foam dissipation time is 2.6~4.5 min, which has excellent endogenous foam suppression effect.

[0082] Table 2 Results of foaming properties of the extract

[0083] Comparative Examples 1 and 3, when filtered only through coarse gauze, could only retain solid medicinal residues. The large water-soluble colloids and free saponins that caused foaming could not be separated and removed, leaving a large amount of foaming base material in the liquid. After homogenization and stirring, these samples easily formed persistent and stable foams, with a total foam height of 32-36 mm. The foam dissipation time exceeded 23 minutes, making them the samples with the most severe foaming tendency and the slowest defoaming speed among all groups. Comparative Example 8, when subjected to high-speed centrifugation alone, failed to remove free saponin colloids from the liquid. The extract exhibited strong foaming, with high foam height and persistent foam that was difficult to dissipate.

[0084] In Comparative Examples 10 and 11-13, the polysaccharide supply in the system was insufficient, failing to fully encapsulate free saponin molecules in the extract. The hydrophobic groups of the saponins were fully exposed, making it easy for stable foam to form after stirring. In Comparative Examples 4 and 7, the curing process was altered, resulting in incomplete complexation between the polysaccharides and the active components, producing only a small amount of antifoaming network colloid. In Comparative Examples 11 and 13, the water-soluble polysaccharides contained in *Polygonatum odoratum* are important endogenous interfacial components in the system, capable of regulating foam behavior and significantly influencing the foam characteristics of the extract.

[0085] 3. MVR Concentration Scaling and Concentration Efficiency As shown in Table 3, the pre-filtration in the examples fully intercepted large molecular scale precursors, and the gradient temperature and pressure were dynamically adjusted with the viscosity of the drug solution to reduce the adhesion of materials on the tube wall. Among them, the heat exchange tube dry scale in Example 3 was only 11.1 g, and the evaporation water volume was 46.0 kg / h, with the lightest scale and the highest concentration efficiency.

[0086] Table 3. Results of MVR Concentration Scaling and Concentration Efficiency Tests

[0087] Comparative Examples 1 and 3 only used coarse filtration with gauze, which could not remove large molecular colloids and suspended aggregates. After the impurities entered the MVR system with the chemical solution, they were dehydrated and coked under the high temperature of the heat exchanger tube walls, continuously adhering and forming a thick organic scale layer. This directly led to a significant decrease in the heat transfer coefficient and a reduction in evaporation efficiency. Comparative Example 1 used a double-effect continuous circulation process, with the material circulating and flushing the heat exchange surface for a long time, resulting in continuous scale accumulation. The dry scale weight reached 36.8 g, and the evaporation rate per unit time was only 27.5 kg / h, the lowest efficiency among all groups. The filtrate of Comparative Examples 8 and 9 contained a certain amount of colloidal impurities, allowing more easily scaled impurities to enter the concentration system.

[0088] Two-stage gradient temperature and pressure matching measures the viscosity change of the extract from thin to thick, maintaining stable heat exchange efficiency and flow rate, and reducing material adhesion and scaling. In Comparative Example 6, as concentration proceeded, the viscosity continuously increased. The fixed temperature and pressure could not adapt to the evaporation characteristics of the high-viscosity material, resulting in a sharp increase in heat exchange resistance. This not only significantly reduced evaporation efficiency but also exacerbated material adhesion and coking on the pipe wall, with the dry scale weight rising to 22.7 g and the evaporation rate per unit time decreasing to 35.8 kg / h.

[0089] 4. Storage stability As shown in Table 4, all examples were Grade 1, and after 30 days of storage, the decoction remained light yellow and clear, without any turbidity or precipitate. The specific ratio of water-soluble polysaccharides from Polygonatum odoratum in this invention can form hydrogen-bonded complexes with buddleja glycosides and polyphenols from Trollius chinensis, isolating oxygen and delaying oxidation; segmented low-temperature decoction and gradient short-time MVR concentration maximize the retention of polyphenolic antioxidants, and the entire formula and process synergistically endow the extract with excellent long-term storage stability.

[0090] Table 4. Stability evaluation of the concentrate after 30 days of storage

[0091] Comparative Examples 1 and 3 were only coarsely filtered through gauze, leaving a large amount of large-molecule colloidal impurities in the solution. With prolonged storage, these impurities flocculated and precipitated. Simultaneously, the lack of polysaccharide protection led to rapid oxidation and browning of flavonoids and polyphenols, resulting in a grade 3 precipitate after storage. In Comparative Example 8, the ionic components continuously compressed the colloidal double layer, gradually weakening the electrostatic stabilization between particles. The nanocolloids continuously collided and aggregated, causing the particle size to continuously increase, ultimately forming a large amount of visible flocculent precipitate, making the concentrate significantly turbid. Comparative Example 10 did not contain Polygonatum odoratum or Nasturtium floridum, and the system lacked endogenous antioxidant polyphenols and polysaccharide carriers. Comparative Example 11 completely removed Polygonatum odoratum, and the absence of a network of colloids to isolate oxygen resulted in rapid oxidative degradation of the active components in both samples. After 30 days of storage, a distinct brownish-red color and a large amount of precipitation appeared, resulting in a grade 3 precipitate.

[0092] 5. Comprehensive performance evaluation of nasal mucosa As shown in Table 5, the duration of ciliary oscillation in the embodiments reached more than 308 minutes. The cilia can maintain normal and regular oscillation for a long time, without causing significant damage to the nasal mucosa, and the mucosal compatibility is excellent.

[0093] Table 5. Results of Cilia Safety Tests

[0094] Comparative Example 10: Ephedrine inhibited nasal ciliary movement; simultaneously, the system lacked Polygonatum odoratum polysaccharide, resulting in a lack of colloidal buffering structure to alleviate irritation, and the normal ciliary movement duration in this group was only 203 min. In Comparative Examples 1 and 3, macromolecular colloidal and proteinaceous impurities in the extracts could not be retained and removed, and the residual impurities continuously stimulated the ciliary epithelial cells, significantly shortening the normal ciliary movement duration. Water-soluble Polygonatum odoratum polysaccharide can form a buffer colloid on the mucosal surface, preventing direct contact between the active components and the mucosa and reducing irritation. In Comparative Example 4, the polysaccharide could not fully complex to form a buffer system; in Comparative Examples 11 and 12, the polysaccharide supply was insufficient, lacking a complete buffering protective structure, leading to increased irritation. In Comparative Example 7, the polysaccharide's complexation reaction with the active component was incomplete, weakening the buffering protective effect.

[0095] like Figure 1 As shown in Table 6, the water-soluble polysaccharide from *Polygonatum odoratum* in Example 1 can form a stable hydrogen-bonded complex network colloid with polyphenols and saponins, restricting the diffusion of active components. It exhibits excellent controlled-release effect in the early stages, releasing only 16.20% in 1 hour, with an increase of only 13.30 percentage points from 1 to 2 hours, without significant burst release, thus avoiding irritation caused by a sudden increase in local drug concentration in the nasal cavity. The release rate is uniform and gradual from 1 to 10 hours, with a stable increase from 4 to 8 hours, until the cumulative release rate reaches 94.80% at 10 hours, at which point the majority of the drug is released.

[0096] Table 6. Cumulative release rate of polyphenols

[0097] Comparative Example 4 lacked a ripening and complexation step, resulting in insufficient formation of the sustained-release colloid. This led to a significant burst release in the early stages, rapid drug release in the early and middle stages, and insufficient long-term efficacy. Comparative Example 11 lacked a Polygonatum odoratum polysaccharide sustained-release carrier, resulting in unconstrained and rapid diffusion of the active component. The most severe burst release occurred at 1 hour, with release approaching saturation at 6 hours, leading to insufficient drug supply in the later stages.

[0098] Comparative Example 10 contains ephedrine, which competitively disrupts the hydrogen bond binding sites between polysaccharides, polyphenols, and saponins, making it difficult to form a stable sustained-release colloid even with the addition of polysaccharides. 43.50% was released at 1 hour, indicating a severe burst release in the early stages; over 74% was released at 4 hours, and 90.20% was released at 8 hours, with minimal increase in release between 8 and 10 hours.

[0099] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A topical traditional Chinese medicine composition for nasal diseases, characterized in that, It is composed of the following components in parts by weight: 260-380 parts of Xanthium sibiricum, 260-380 parts of Centipeda minima, 220-380 parts of Patchouli, 120-240 parts of Chrysanthemum indicum, 100-170 parts of Perilla frutescens stem, 70-150 parts of Polygonatum odoratum, and 55-110 parts of Trollius chinensis.

2. The topical traditional Chinese medicine composition for nasal diseases according to claim 1, characterized in that, The total water-soluble polysaccharide content in the Polygonatum odoratum is ≥9% by mass; the total polyphenol content in the Nasturtium floridum is ≥2.2% by mass.

3. The topical traditional Chinese medicine composition for nasal diseases according to claim 1, characterized in that, The total saponin content of the herb *Centipeda minima* is above 2%.

4. The application of a topical traditional Chinese medicine composition for nasal diseases according to any one of claims 1 to 3, characterized in that, Used to prepare drugs for rhinitis, nasal mucosal inflammation, and nasal dryness and damage.

5. An extract of a topical traditional Chinese medicine composition for nasal diseases, characterized in that, It is prepared from the topical Chinese medicine composition for nasal diseases as described in any one of claims 1 to 3.

6. A method for preparing an extract of the topical traditional Chinese medicine composition for nasal diseases according to claim 5, characterized in that, Includes the following steps: S1. Segmented and sealed decoction: First, add water to the cocklebur, centipeda minima and polygonatum and decoct; then add patchouli, wild chrysanthemum, perilla stem and golden lotus and decoct together, and collect the decoction. S2. Clarification Pretreatment: After cooling the decoction, adjust the pH, add chitosan and stir to flocculate, then centrifuge to remove colloids, free saponins and colloidal aggregates to obtain a clarified extract and keep it warm for storage. S3. Segmented gradient MVR concentration: The clarified extract after heat preservation is concentrated by segmented gradient MVR evaporation, and the heating residence time is controlled. After the concentrate is matured, the extract of the topical Chinese medicine composition for nasal diseases is obtained.

7. The method for preparing the extract of the topical traditional Chinese medicine composition for nasal diseases according to claim 6, characterized in that, When decocting S1, the mass of water added should be 9 to 11 times the total mass of the topical Chinese medicine composition for nasal diseases; decoct at 90 to 98℃ for 1.5 to 2 hours first, and then decoct again at 85 to 92℃ for 20 to 35 minutes.

8. The method for preparing the extract of the topical traditional Chinese medicine composition for nasal diseases according to claim 6, characterized in that, In S2, the amount of chitosan added is 0.03%~0.06% of the decoction mass, and the centrifugation speed is 8000~10000 r / min.

9. The method for preparing the extract of the topical traditional Chinese medicine composition for nasal diseases according to claim 6, characterized in that, S3 is divided into two-stage gradient concentration: the first stage temperature is 70~80℃, and the second stage temperature is 65~75℃, with the first stage concentration temperature being higher than the second stage concentration temperature; the heating residence time does not exceed 20 min.

10. The method for preparing the extract of the topical traditional Chinese medicine composition for nasal diseases according to claim 9, characterized in that, When the relative density of the concentrated liquid at 50℃ is 1.06~1.10, it is transferred to a sealed, heat-insulated maturation tank and allowed to stand at 58~62℃ for 40~60 minutes.

Images