Traditional Chinese and western medicine combined male function improving composition and preparation method thereof

Abstract

The invention belongs to the field of pharmaceutical preparations, and provides a Chinese and western medicine combined male function improving composition and a preparation method thereof. According to the invention, three active components, namely sildenafil citrate, icariin and fried Chinese chive seed powder, are synergistically designed, the sildenafil citrate and icariin are used for preparing clathrate compound powder through a beta-cyclodextrin clathrate solubilizing technology, the fried Chinese chive seed powder is micronized and then dispersed in a film forming solution under the wetting action of polysorbate 80, and the film forming solution is prepared into the sildenafil-icariin clathrate compound. A hydroxypropyl methylcellulose-sodium carboxymethyl cellulose double-polymer film base material system and a citric acid-trisodium citrate buffer stable system are combined, so that the technical problems that a multi-component system is poor in film forming uniformity under high solid content load, the mechanical integrity of the film is insufficient, and instant release and structural stability are difficult to consider at the same time are solved; the traditional Chinese medicine composition has the advantages of convenience in taking, quick response and high bioavailability, and is suitable for improving male functions.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, specifically to a combination of traditional Chinese and Western medicine for improving male function and its preparation method. Background Technology

[0002] Erectile dysfunction (ED) is a common health problem affecting men's quality of life, and its incidence is increasing year by year due to the accelerating aging of the population and increasing life pressure. In clinical applications, phosphodiesterase type 5 inhibitors such as sildenafil citrate have become first-line treatment drugs due to their definite efficacy. However, traditional oral tablets have problems such as long onset time, first-pass effect leading to reduced bioavailability, and the need to take the medication in advance, affecting the convenience of use. Icariin, a classic active ingredient in traditional Chinese medicine for tonifying the kidney and strengthening yang, has the effect of improving sexual function and enhancing physical fitness, but its poor water solubility limits its absorption efficiency. In addition, roasted leek seed powder is a traditional Chinese medicine powder for warming the kidney and assisting yang, with a basis for applications such as consolidating essence and assisting yang. However, its powder is generally insoluble in water, and particle size and dispersion stability have a significant impact on the appearance, taste, and content uniformity of oral instant film, which urgently needs to be co-designed with instant film-forming systems. Oral mucosal fast-dissolving films, as a novel drug delivery system, can be directly absorbed through the oral mucosa, avoiding the first-pass effect of the liver, significantly shortening the onset time, and improving bioavailability. They also offer advantages such as convenient portability, discreet administration, and good patient compliance, providing an ideal technological platform for overcoming the limitations of traditional dosage forms. Developing oral fast-dissolving film formulations that combine the rapid onset of Western medicine with the gentle conditioning effects of traditional Chinese medicine is of great significance for meeting users' application needs for rapid functional improvement, enhanced user experience, and long-term safe use.

[0003] Currently, research on oral instant-dissolving film formulations mainly focuses on loading single water-soluble active ingredients. The development of multi-component oral films, especially those containing compound traditional Chinese and Western medicines or poorly soluble drugs, still faces numerous technical challenges. For example, Chinese patent CN107468672A discloses a sildenafil oral instant-dissolving film and its preparation method, but it suffers from limitations in the function of a single active ingredient and fails to address the problem of limited drug loading due to low drug solubility. In existing technologies, when multiple active substances such as sildenafil citrate, icariin, and roasted leek seed powder are simultaneously loaded, the large differences in solubility of each component lead to phase separation or crystallization in the film-forming solution, resulting in uneven film appearance, poor content uniformity, low mechanical strength, and unstable instant-dissolving performance. Furthermore, multi-component high-solids-content film-forming systems are prone to processing defects such as residual bubbles, uneven thickness, and edge curling during defoaming, casting, and drying. Moreover, there is a lack of systematic optimization schemes for moisture control, residual solvent management, and maintenance of active ingredient stability during film storage. Summary of the Invention

[0004] The purpose of this invention is to provide a combination of traditional Chinese and Western medicine for improving male function, which solves the technical contradictions of current multi-component film-forming systems in terms of coating uniformity and degassing processing window under high solid content and powder load, film mechanical integrity and low moisture and low residual solute storage stability, as well as rapid wetting and dissolution release and inclusion complex structure maintenance and content uniformity.

[0005] This invention constructs a β-cyclodextrin inclusion solubilization system of sildenafil citrate and icariin, and introduces roasted leek seed powder into an oral mucosa fast-dissolving film system via micronization and wetting dispersion. Combined with a synergistic film-forming substrate of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose, a citrate-trisodium citrate buffer stabilization system, and optimized casting and drying process parameters, this invention achieves efficient loading, rapid release, and stable retention of poorly soluble active ingredients of traditional Chinese and Western medicines in an oral mucosa fast-dissolving film. The components exhibit synergistic effects in multiple stages such as solubilization, film formation, wetting, and disintegration, thereby improving the overall performance and applicability of the film.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A combination of traditional Chinese and Western medicine for improving male sexual function, comprising, by weight percentage, the total solid components in the dry film of the composition: (a) Sildenafil citrate 0.5–5.0%; (b) Icariin 0.1–3.0%; (c) Total β-cyclodextrin 10–40%; wherein the total β-cyclodextrin includes β-cyclodextrin for forming sildenafil citrate-β-cyclodextrin inclusion complex and β-cyclodextrin for forming icariin-β-cyclodextrin inclusion complex. (d) Hydroxypropyl methylcellulose 10–60%; (e) Sodium carboxymethyl cellulose 5–40%; (f) Glycerin 5–25%; (g) Polysorbate 80 0.05–2.0%; (h) Citric acid 0.05–3.0%; (i) Trisodium citrate dihydrate 0.05–3.0%; (j) 30–50% roasted leek seed powder; The composition comprises: a sildenafil citrate-β-cyclodextrin inclusion complex powder formed from sildenafil citrate and β-cyclodextrin, an icariin-β-cyclodextrin inclusion complex powder formed from icariin and β-cyclodextrin, a film substrate formed from hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and glycerol, a citrate-trisodium citrate buffer system, and roasted leek seed powder.

[0007] Furthermore, in the sildenafil citrate-β-cyclodextrin inclusion complex, the molar ratio of β-cyclodextrin to sildenafil citrate is 1.0:(0.5-1.2), and in the icariin-β-cyclodextrin inclusion complex, the molar ratio of β-cyclodextrin to icariin is 1.0:(0.1–1.2).

[0008] Furthermore, the sildenafil citrate-β-cyclodextrin inclusion complex powder is prepared through the following steps: A1. Raw material preparation: Mix 100–300 parts by weight of β-cyclodextrin, 50–250 parts by weight of sildenafil citrate, and 300–3000 parts by weight of deionized water to make the molar ratio of β-cyclodextrin to sildenafil citrate 1.0:(0.5–1.2); A2. Inclusion reaction: The β-cyclodextrin was added to the deionized water and stirred at 40–60°C for 0.5–1.5 h; after adding the sildenafil citrate, stirring was continued at 25–50°C for 1–6 h. A3. Post-processing: The slurry obtained in step A2 is concentrated under reduced pressure at an absolute pressure of 0.01–0.05 MPa; then dried at 30–80 °C for 4–12 h to obtain the sildenafil citrate-β-cyclodextrin inclusion complex powder. A4. Endpoint Criteria and Quality Control: The moisture content of the sildenafil citrate-β-cyclodextrin inclusion complex powder is ≤5.0wt%, and the sildenafil citrate content in the sildenafil citrate-β-cyclodextrin inclusion complex powder is 20–50wt%.

[0009] Furthermore, the icariin-β-cyclodextrin inclusion complex powder is prepared through the following steps: B1. Raw material preparation: Mix 100–400 parts by weight of β-cyclodextrin, 10–200 parts by weight of icariin, 100–2000 parts by weight of anhydrous ethanol and 300–3000 parts by weight of deionized water, so that the molar ratio of β-cyclodextrin to icariin is 1.0:(0.1–1.2); B2. Inclusion reaction: The β-cyclodextrin was added to the deionized water and stirred at 40–60°C for 0.5–1.5 h; the icariin was added to the anhydrous ethanol and stirred at 20–40°C for 0.2–1.0 h; the ethanol solution of the icariin was added dropwise to the aqueous solution of the β-cyclodextrin at a dropping rate of 0.5–10 mL / min and stirred at 25–50°C for 1–6 h. B3. Post-processing: The mixture obtained in step B2 was subjected to de-alcoholization under reduced pressure of 0.01–0.05 MPa absolute pressure; then dried at 30–80 °C for 4–12 h to obtain icariin-β-cyclodextrin inclusion complex powder. B4. Endpoint Criteria and Quality Control: The residual ethanol content of the icariin-β-cyclodextrin inclusion complex powder is ≤5000ppm, the moisture content of the icariin-β-cyclodextrin inclusion complex powder is ≤5.0wt%, and the icariin content in the icariin-β-cyclodextrin inclusion complex powder is 5–30wt%.

[0010] Furthermore, the citric acid-trisodium citrate buffer solution is prepared by the following steps: C1. Raw material preparation: Mix 1–50 parts by weight of citric acid, 1–100 parts by weight of trisodium citrate dihydrate, and 100–2000 parts by weight of deionized water; C2. Dissolve the citric acid and the trisodium citrate dihydrate in the deionized water and stir at 20–40°C for 0.2–1.0 h to obtain a citric acid-trisodium citrate buffer solution; C3. Endpoint Criteria and Quality Control: The pH of the citric acid-trisodium citrate buffer solution is 5.0–7.0.

[0011] Furthermore, the thin film substrate solution of the composition is prepared by the following steps: D1. Raw material preparation: Weigh 10–60 parts by weight of hydroxypropyl methylcellulose, 5–40 parts by weight of sodium carboxymethyl cellulose, 5–25 parts by weight of glycerol and 300–2000 parts by weight of deionized water. D2. Hydroxypropyl methylcellulose and sodium carboxymethyl cellulose are added to deionized water and stirred at 20–40°C for 1–6 h to obtain a homogeneous polymer solution, wherein the total mass fraction of the polymer is 2–10 wt% of the total mass of the solution, based on the combined mass of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose. D3. Add the glycerol to the polymer solution obtained in step D2, stir at 20–40°C for 0.2–1.0 h, and degas under reduced pressure for 0.5–2.0 h, wherein the reduced pressure is an absolute pressure of 0.01–0.05 MPa, to obtain the film substrate solution; D4. Quality control: The pH of the thin film substrate solution is 5.0–7.0.

[0012] Furthermore, the dry film thickness of the composition is 30–200 μm, the film composition is cut into single-piece dosing units with an area of ​​2–12 cm², and the oral mucosa fast-dissolving film composition does not use gelatin as a film-forming material. The dissolution (disintegration) time of the oral mucosa rapid-dissolving film was determined by measuring it in purified water at 37°C, and the dissolution time was 10–120 s.

[0013] As a concept of this invention, this invention adopts a multi-component synergistic design of sildenafil citrate, icariin and roasted leek seed powder. The inclusion complex powder is prepared by combining sildenafil citrate and icariin with β-cyclodextrin inclusion solubilization technology. The roasted leek seed powder is micronized and introduced into the film-forming system by wetting and dispersion. It is mainly used to enhance the drug loading capacity, release rate and bioavailability of oral fast-dissolving films. Sildenafil citrate, as a phosphodiesterase type 5 inhibitor, has a clear effect on improving erectile function, but its solubility in water is limited, and direct dispersion in film-forming solution easily leads to crystallization and uneven content. Icariin, as an active ingredient of flavonoid traditional Chinese medicine, has extremely poor water solubility, making it difficult for conventional preparations to achieve effective absorption. Roasted leek seed powder, as a traditional Chinese medicine powder for warming the kidneys and invigorating yang, has its effective material basis rapidly disintegrated and released with the film matrix, forming a fine powder dispersion that can be absorbed through the oral mucosa or after swallowing. Together with icariin, it embodies the conditioning characteristics of traditional Chinese medicine compound prescriptions. Through β-cyclodextrin inclusion technology, hydrophobic drug molecules are embedded inside the cyclodextrin cavity to form a water-soluble inclusion complex, which significantly improves the apparent solubility and dissolution rate of the active ingredient. At the same time, the inclusion effect stabilizes the conformation of the drug molecule and reduces the tendency for degradation and crystallization during the film-forming and drying process. The synergistic design of multiple active ingredients fully leverages the respective advantages of rapid onset of Western medicine and gentle conditioning of traditional Chinese medicine. Sildenafil citrate rapidly improves the relaxation of corpus cavernosum smooth muscle by inhibiting phosphodiesterase type 5, while icariin enhances overall function through multiple target pathways, including promoting nitric oxide synthesis, improving endothelial function, and regulating sex hormone levels. The three ingredients complement each other in terms of duration of action, mechanism of action, and safety, improving the comprehensiveness and durability of the effect. By controlling the molar ratio of β-cyclodextrin to sildenafil citrate within the range of 1.0:(0.5-1.2) and the molar ratio of β-cyclodextrin to icariin within the range of 1.0:(0.1-1.2), sufficient inclusion efficiency is ensured while avoiding problems such as excessively high viscosity of the film-forming solution and decreased film toughness caused by excessive cyclodextrin, thus achieving the optimal balance between drug loading and film-forming performance.

[0014] This invention also discloses a method for preparing a male function improvement composition combining traditional Chinese and Western medicine as described in the preceding claims, comprising the following steps: S1. Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder; S2. Preparation of icariin-β-cyclodextrin inclusion complex powder; S3. Prepare a citric acid-trisodium citrate buffer solution; S4. At 20–40°C, sildenafil citrate-β-cyclodextrin inclusion complex powder and icariin-β-cyclodextrin inclusion complex powder are added to a film substrate solution, along with polysorbate 80, roasted leek seed powder, and a citrate-trisodium citrate buffer solution. The amounts of the sildenafil citrate-β-cyclodextrin inclusion complex powder added are 0.5–5.0 parts by weight (calculated as sildenafil citrate), 0.1–3.0 parts by weight (calculated as icariin), 30–50 parts by weight of roasted leek seed powder, 0.05–2.0 parts by weight of polysorbate 80, and 5–50 parts by weight of the citrate-trisodium citrate buffer solution. The mixture is stirred for 0.5–2.0 h to obtain a film-forming solution. S5. The film-forming solution obtained in step S4 is cast into a film using a doctor blade with a gap of 100–800 μm; then dried at 30–60°C for 10–60 min to obtain a dry film, wherein the thickness of the dry film is 30–200 μm, and the oral mucosa fast-dissolving film composition does not use gelatin as a film-forming material. S6. Cut the dry film obtained in step S5 to obtain the oral mucosa fast-dissolving film composition, wherein the dry film is cut into single-piece dosing units and the area of ​​the single-piece dosing unit is 2–12 cm². The mass ratio of hydroxypropyl methylcellulose to sodium carboxymethyl cellulose is 1.0:0.2–2.0.

[0015] Further, after step S4, the film-forming liquid is subjected to degassing under reduced pressure, with a degassing pressure of 0.01–0.05 MPa and a degassing time of 0.2–2.0 h; the moisture content of the film composition after drying in step S5 is ≤8.0 wt%; and the residual ethanol content of the film composition after drying in step S5 is ≤5000 ppm.

[0016] Furthermore, the single-piece dosing unit described in step S6 is packaged in an aluminum-plastic composite package; The encapsulated film is stored at 2–30°C.

[0017] As another aspect of this invention, roasted leek seed powder is further introduced as a conditioning component in a traditional Chinese medicine compound. Given that leek seed powder is insoluble or poorly soluble in water and easily produces a grainy texture, this invention micronizes and sieves the roasted leek seed powder (e.g., passing it through a 300-mesh sieve or ensuring D90 ≤ 50 μm), and disperses it in a film-forming solution under the wetting effect of polysorbate 80. This avoids fluctuations in content uniformity and rough film surface caused by powder agglomeration and sedimentation. Simultaneously, the roasting process helps reduce the irritation of raw powder and improves the taste. As another aspect of this invention, a hydroxypropyl methylcellulose and sodium carboxymethyl cellulose dual-polymer synergistic film-forming substrate system combined with a citric acid-trisodium citrate buffer stabilization system and an optimized casting and drying process design is used primarily to enhance the film-forming uniformity, mechanical strength, instant solubility, and storage stability of oral instant films. Hydroxypropyl methylcellulose (HMC), a nonionic water-soluble polymer, possesses excellent film-forming properties and flexibility. However, when used alone, the film is prone to absorbing moisture and softening, resulting in insufficient mechanical strength. Sodium carboxymethyl cellulose (SMC), an anionic polymer, can significantly enhance the tensile strength and disintegration rate of the film, but excessive use can lead to increased brittleness and decreased solubility. By optimizing the mass ratio of HMC to SMC within the range of 1.0:0.2-2.0, the two polymers exhibit synergistic effects in molecular chain entanglement, hydrogen bonding, and hydration layer formation. This ensures a balance between the film's mechanical strength and flexibility while maintaining its rapid wetting and disintegration properties. Glycerin, as a plasticizer, lowers the energy barrier of chain segment movement by intercalating between polymer molecular chains, enhancing the film's softness and crack resistance. Simultaneously, the moisturizing effect of an appropriate amount of glycerin helps maintain a stable moisture content in the film during storage, preventing brittleness caused by excessive drying. The citric acid-trisodium citrate buffer system stabilizes the pH of the film-forming solution and the film within the range of 5.0-7.0, ensuring the chemical stability of the active ingredients while adapting to the physiological pH of the oral mucosa, reducing irritation. Simultaneously, the citrate ions in the buffer system can form ionic interactions with the polymer, further enhancing the structural stability of the film. By controlling process parameters such as the scraping gap, drying temperature, and time, precise control of film thickness, effective removal of moisture and residual solvents, and preservation of the integrity of the inclusion complex structure are achieved, ensuring the product's quality uniformity and long-term stability.

[0018] The sildenafil citrate-β-cyclodextrin inclusion complex and the icariin-β-cyclodextrin inclusion complex exhibit a significant synergistic effect in the oral rapid-dissolving film system of this invention. Roasted leek seed powder participates in film disintegration and dispersion system formation through micronization and wetting dispersion, and provides supplementary conditioning from the traditional Chinese medicine compound. The sildenafil citrate inclusion complex focuses on rapid solubilization and immediate release, increasing drug solubility by 2-6 times through cyclodextrin inclusion, rapidly releasing the active ingredient upon contact with the oral mucosa, achieving rapid onset of action within 10-15 minutes; the icariin inclusion complex focuses on stable solubilization and sustained release, protecting flavonoid glycoside bonds from enzymatic degradation and pH fluctuations through cyclodextrin inclusion, improving its bioavailability and prolonging the duration of efficacy. Regarding improved rapid dissolution, the rapid hydration and disintegration of the sildenafil inclusion complex created initial conditions for rapid overall film wetting, while the enhanced hydrophilicity of the icariin inclusion complex further accelerated water penetration into the film. The synergistic effect of these two compounds shortened the film's rapid dissolution and disintegration time to 10-120 seconds, significantly better than the 150-300 seconds of a single inclusion complex system. In terms of ensuring content uniformity, the two inclusion complex powders have similar particle size distributions and densities, resulting in consistent suspension stability and sedimentation rates in the film-forming solution. This avoids uneven content caused by powder stratification. Simultaneously, the inclusion structure inhibits drug migration and recrystallization during drying, ensuring uniform distribution of active ingredients throughout the film. In terms of synergistic effects, sildenafil citrate rapidly improves hemodynamics by inhibiting phosphodiesterase type 5, while icariin enhances long-term sexual function by promoting the expression of endothelial nitric oxide synthase, scavenging oxygen free radicals, and regulating sex hormone levels. The two complement each other in terms of onset time and target of action, achieving the dual effects of rapid improvement and continuous conditioning, thus improving user satisfaction and compliance.

[0019] Beneficial technical effects 1. Significantly enhances the drug loading capacity and bioavailability of poorly soluble active ingredients: Sildenafil citrate and icariin are converted into a water-soluble inclusion complex using β-cyclodextrin inclusion technology. The apparent solubility of the active ingredients in the film-forming solution is increased by 2-6 times. The drug loading of the film reaches the effective content range of 0.5-5.0% sildenafil and 0.1-3.0% icariin. Oral mucosal absorption avoids the first-pass effect of the liver. The bioavailability is increased by 40-60% compared with traditional oral tablets, realizing the efficient loading and rapid absorption of poorly soluble Chinese and Western medicine compound in fast-dissolving films.

[0020] 2. Achieving a balance between uniformity and stability in multi-component film-forming systems: By using a synergistic film-forming substrate system of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose dual polymers, with a mass ratio optimized within the range of 1.0:0.2-2.0, combined with glycerol plasticizer and citrate-trisodium citrate buffer stabilization, the film tensile strength reaches 3-8 MPa, the elongation at break reaches 30-80%, the thickness uniformity RSD ≤ 5%, the inclusion complex powder is uniformly dispersed in the film-forming solution and does not recrystallize after drying, and the content uniformity meets the requirements of the 10-tablet method in the pharmacopoeia. This solves the technical problems of uneven film formation, poor mechanical properties, and large content fluctuations in multi-component high-solids-content systems.

[0021] 3. Achieving a balance between rapid wetting, dissolution, and release and structural integrity: By optimizing process parameters such as the coating gap of 100-800 micrometers, drying temperature of 30-60℃, and drying time of 10-60 minutes, an oral fast-dissolving film with a dry film thickness of 30-200 micrometers, a moisture content of ≤8.0%, and ethanol residue of ≤5000ppm was prepared. The film dissolves rapidly in pure water at 37℃ in 10-120 seconds, completely wetting within 5 seconds and completely disintegrating within 120 seconds. The active ingredients are released cumulatively at >85% within 3 minutes. At the same time, the film maintains good stability for 6 months under storage conditions of 2-30℃, the inclusion complex structure remains intact, and the active ingredient content retention rate is >95%, thus meeting the dual requirements of rapid onset of action and long-term stability.

[0022] 4. Improve patient convenience and treatment adherence: The film is cut into single-dose units with an area of ​​2-12 square centimeters, making it easy to carry and take discreetly. It does not require water to take and dissolves naturally after being applied to the oral mucosa. This avoids the inconveniences of traditional tablets, such as difficulty in swallowing, delayed onset of action, and the need to take the medication in advance. The onset time is shortened to 10-20 minutes, which is 20-30 minutes earlier than conventional preparations. This significantly improves the medication experience and increases long-term treatment adherence and satisfaction.

[0023] 5. Achieving synergistic effects and optimized safety of traditional Chinese and Western medicine: The synergistic combination of sildenafil citrate, icariin, and roasted leek seed powder allows the Western medicine to rapidly improve hemodynamics, while the traditional Chinese medicine gently regulates endothelial function and hormone levels. This results in a complementary effect in terms of duration of action, target of action, and adverse reaction spectrum, with synergistic improvement superior to single-component formulations. Furthermore, absorption through the oral mucosa reduces gastrointestinal irritation and liver burden. It does not contain animal-derived excipients such as gelatin, making it suitable for vegetarians and patients with specific religious beliefs, significantly improving safety and applicability. Attached Figure Description

[0024] Figure 1 The images are X-ray powder diffraction (XRPD) patterns of Example 1 and Comparative Example 5 of the present invention.

[0025] Figure 2 The Fourier transform infrared (FTIR) spectra of Embodiment 1 and Comparative Example 5 of the present invention are shown.

[0026] Figure 3 The diagram shows the dynamic light scattering particle size probability density distribution of Embodiment 1 and Comparative Example 4 of the present invention.

[0027] Figure 4 This is a dynamic light scattering particle size cumulative distribution diagram of Example 1 and Comparative Example 4 of the present invention.

[0028] Figure 5 The X-ray photoelectron spectroscopy N1s combination spectrum of Example 1 and Comparative Example 8 of the present invention.

[0029] Figure 6 The X-ray photoelectron spectroscopy (O1s) combination spectra of Example 1 and Comparative Example 8 of the present invention are shown. Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0031] Example 1 This embodiment provides a combination of traditional Chinese and Western medicine to improve male function, which exists in the form of a fast-dissolving film on the oral mucosa.

[0032] Composition of the composition: Based on the total mass of the solid components in the dry film of the composition of this embodiment, and expressed as a percentage by mass, it includes: [unclear text - possibly a product name or ingredient] Nafedipine citrate 3.0%, icariin 2.0%, roasted leek seed powder 40.0%, total β-cyclodextrin 17.0%, hydroxypropyl methylcellulose 18.0%, sodium carboxymethyl cellulose 12.0%, glycerol 6.0%, polysorbate 80 0.8%, citric acid 0.4%, trisodium citrate dihydrate 0.8%.

[0033] The composition of this embodiment comprises: a sildenafil citrate-β-cyclodextrin inclusion complex powder formed from sildenafil citrate and β-cyclodextrin, an icariin-β-cyclodextrin inclusion complex powder formed from icariin and β-cyclodextrin, a film substrate formed from hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and glycerol, a citrate-trisodium citrate buffer system, and roasted leek seed powder.

[0034] Molar ratio relationship: In this embodiment, the molar ratio of β-cyclodextrin to sildenafil citrate is 1.0:0.57, and the molar ratio of β-cyclodextrin to icariin is 1.0:0.42.

[0035] Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder: A1. Raw material preparation: 200 parts by weight of β-cyclodextrin, 66.9 parts by weight of sildenafil citrate, and 1500 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to sildenafil citrate in this embodiment 1.0:0.57; A2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment and stirred at 50°C for 1.0 h; after adding the sildenafil citrate of this embodiment, stirring was continued at 38°C for 3.5 h; A3. Post-processing: The slurry obtained in step A2 was concentrated under reduced pressure (absolute pressure 0.03 MPa); then dried at 55°C for 8 hours to obtain the sildenafil citrate-β-cyclodextrin inclusion complex powder of this embodiment. A4. Endpoint Criteria and Quality Control: The moisture content of the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 3.5 wt%, and the sildenafil citrate content in the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 25 wt%.

[0036] Preparation of icariin-β-cyclodextrin inclusion complex powder: B1. Raw material preparation: 250 parts by weight of β-cyclodextrin, 62.5 parts by weight of icariin, 1000 parts by weight of anhydrous ethanol, and 1500 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to icariin in this embodiment 1.0:0.42; B2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment and stirred at 50°C for 1.0 h; the icariin of this embodiment was added to the anhydrous ethanol of this embodiment and stirred at 30°C for 0.6 h; the ethanol solution of icariin of this embodiment was added dropwise to the aqueous solution of β-cyclodextrin of this embodiment at a dropping rate of 5 mL / min, and stirring was continued at 38°C for 3.5 h; B3. Post-processing: The mixture obtained in step B2 was subjected to depressurized removal alcohol, with a depressurization pressure of 0.03 MPa absolute pressure; subsequently, it was dried at 55°C for 8 hours to obtain the icariin-β-cyclodextrin inclusion complex powder of this embodiment; B4. Endpoint Criteria and Quality Control: The residual ethanol content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 3000 ppm, the moisture content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 3.5 wt%, and the icariin content in the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 20 wt%.

[0037] Preparation of citric acid-trisodium citrate buffer solution: C1. Raw material preparation: Mix 25 parts by weight of citric acid, 50 parts by weight of trisodium citrate dihydrate, and 1000 parts by weight of deionized water; C2. The citric acid and trisodium citrate dihydrate of this embodiment are dissolved in the deionized water of this embodiment, and stirred at 30°C for 0.6 h to obtain a citric acid-trisodium citrate buffer solution; C3. Endpoint Criteria and Quality Control: The pH of the citric acid-trisodium citrate buffer solution in this embodiment is 6.0.

[0038] Thin film substrate solution preparation: D1. Raw material preparation: Weigh out 18 parts by weight of hydroxypropyl methylcellulose, 12 parts by weight of sodium carboxymethyl cellulose, 6 parts by weight of glycerol, and 1000 parts by weight of deionized water; D2. Hydroxypropyl methylcellulose and sodium carboxymethyl cellulose were added to deionized water and stirred at 30°C for 3.5 h to obtain a homogeneous polymer solution, wherein the total mass fraction of the polymer was 2.9 wt% of the total mass of the solution, consisting of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose. D3. Add glycerol of this embodiment to the polymer solution obtained in step D2, stir at 30°C for 0.6 h, and degas under reduced pressure for 1.2 h. The reduced pressure in this embodiment is 0.03 MPa absolute pressure, to obtain the film substrate solution of this embodiment; D4. Quality control: The pH of the thin film substrate solution in this embodiment is 6.0.

[0039] Preparation method of the composition: S1. Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder; S2. Preparation of icariin-β-cyclodextrin inclusion complex powder; S3. Prepare a citric acid-trisodium citrate buffer solution; S4. At 30℃, 12 parts by weight of sildenafil citrate-β-cyclodextrin inclusion complex powder and 10.0 parts by weight of icariin-β-cyclodextrin inclusion complex powder were added to the above film substrate solution, along with 40.0 parts by weight of roasted leek seed powder (passed through a 300-mesh sieve) to make the roasted leek seed powder content in the dry film 40.0%. 0.8 parts by weight of polysorbate 80 were added, along with 17.2 parts by weight of citric acid-trisodium citrate buffer solution. The mixture was stirred for 1.2 hours to obtain the film-forming solution. The film-forming solution of this embodiment was subjected to degassing under reduced pressure. The degassing pressure was 0.03 MPa absolute, and the degassing time was 1.0 h. S5. The film-forming solution obtained in step S4 is cast into a film. In this embodiment, the film-forming is done using a doctor blade with a blade gap of 450 μm. The film is then dried at 45°C for 35 min to obtain a dry film. The dry film thickness in this embodiment is 100 μm. Furthermore, the oral mucosa quick-dissolving film composition in this embodiment does not use gelatin as a film-forming material. The moisture content of the dried film composition in this embodiment is 6.5 wt%. The residual ethanol content of the dried film composition in this embodiment is 3000 ppm. S6. The dry film obtained in step S5 is cut to obtain the oral mucosa fast-dissolving film composition of this embodiment, wherein the dry film of this embodiment is cut into single-piece dosing units and the area of ​​a single-piece dosing unit of this embodiment is 7cm²; In this embodiment, the single-dose unit is packaged in an aluminum-plastic composite package; the packaged film in this embodiment is stored at 16°C.

[0040] In this embodiment, the mass ratio of hydroxypropyl methylcellulose to sodium carboxymethyl cellulose is 1.0:0.67.

[0041] The dissolution (disintegration) time of the oral mucosa rapid-dissolving film in this embodiment was determined by measuring it in purified water at 37°C, and the dissolution time was 60 seconds.

[0042] Features of Example 1: This example uses a formulation with a moderate content of active ingredients: 3.0% sildenafil citrate, 2.0% icariin, 40.0% roasted leek seed powder, and a total β-cyclodextrin content of 17.0%, ensuring good inclusion efficiency and stability. The combination of 18.0% hydroxypropyl methylcellulose and 12.0% sodium carboxymethyl cellulose provides moderate film-forming properties and mechanical strength, while 6.0% glycerol ensures good film flexibility. Process parameters were selected under mild conditions: inclusion reaction temperature 38℃ and drying temperature 45-55℃, ensuring process stability and reproducibility. The design of a film thickness of 100μm, a single-sheet area of ​​7cm², and a rapid dissolution time of 60s balances drug loading and rapid release characteristics. This formulation is stable and reliable, suitable for daily health care applications to improve male function, especially suitable for users who require a certain onset time but do not require extremely rapid dissolution. It can be stored for a long time at room temperature or under refrigeration.

[0043] Example 2 This embodiment provides a combination of traditional Chinese and Western medicine to improve male function, which exists in the form of a fast-dissolving film on the oral mucosa.

[0044] Composition of the composition: Based on the total mass of the solid components in the dry film of the composition of this embodiment, and expressed as a percentage by mass, it includes: 5.0% sildenafil citrate, 3.0% icariin, 30.0% roasted leek seed powder, 27.3% total β-cyclodextrin, 18.0% hydroxypropyl methylcellulose, 10.0% sodium carboxymethyl cellulose, 5.0% glycerol, 0.6% polysorbate 80, 0.33% citric acid, and 0.77% trisodium citrate dihydrate.

[0045] The composition of this embodiment comprises: a sildenafil citrate-β-cyclodextrin inclusion complex powder formed from sildenafil citrate and β-cyclodextrin, an icariin-β-cyclodextrin inclusion complex powder formed from icariin and β-cyclodextrin, a film substrate formed from hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and glycerol, a citrate-trisodium citrate buffer system, and roasted leek seed powder.

[0046] Molar ratio relationship: In this embodiment, the molar ratio of β-cyclodextrin to sildenafil citrate is 1.0:0.50, and the molar ratio of β-cyclodextrin to icariin is 1.0:0.49.

[0047] Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder: A1. Raw material preparation: 280 parts by weight of β-cyclodextrin, 82 parts by weight of sildenafil citrate, and 2500 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to sildenafil citrate in this embodiment 1.0:0.50; A2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment, and stirred at 58°C for 1.3 h; after adding the sildenafil citrate of this embodiment, stirring was continued at 45°C for 5.0 h; A3. Post-processing: The slurry obtained in step A2 was concentrated under reduced pressure (absolute pressure 0.02 MPa); then dried at 70°C for 10 h to obtain the sildenafil citrate-β-cyclodextrin inclusion complex powder of this embodiment. A4. Endpoint Criteria and Quality Control: The moisture content of the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 2.8 wt%, and the sildenafil citrate content in the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 22.7 wt%.

[0048] Preparation of icariin-β-cyclodextrin inclusion complex powder: B1. Raw material preparation: 350 parts by weight of β-cyclodextrin, 101.6 parts by weight of icariin, 1600 parts by weight of anhydrous ethanol, and 2500 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to icariin in this embodiment 1.0:0.49; B2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment and stirred at 58°C for 1.3 h; the icariin of this embodiment was added to the anhydrous ethanol of this embodiment and stirred at 35°C for 0.8 h; the ethanol solution of icariin of this embodiment was added dropwise to the aqueous solution of β-cyclodextrin of this embodiment at a dropping rate of 8 mL / min, and stirring was continued at 45°C for 5.0 h; B3. Post-processing: The mixture obtained in step B2 was subjected to depressurized removal alcohol, with a depressurization pressure of 0.02 MPa absolute pressure; subsequently, it was dried at 70°C for 10 h to obtain the icariin-β-cyclodextrin inclusion complex powder of this embodiment; B4. Endpoint Criteria and Quality Control: The residual ethanol content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 4200 ppm, the moisture content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 2.8 wt%, and the icariin content in the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 22.5 wt%.

[0049] Preparation of citric acid-trisodium citrate buffer solution: C1. Raw material preparation: Mix 15 parts by weight of citric acid, 35 parts by weight of trisodium citrate dihydrate, and 800 parts by weight of deionized water; C2. The citric acid and trisodium citrate dihydrate of this embodiment are dissolved in the deionized water of this embodiment, and stirred at 35°C for 0.8 h to obtain a citric acid-trisodium citrate buffer solution; C3. Endpoint Criteria and Quality Control: The pH of the citric acid-trisodium citrate buffer solution in this embodiment is 6.5.

[0050] Thin film substrate solution preparation: D1. Raw material preparation: Weigh out 18 parts by weight of hydroxypropyl methylcellulose, 10 parts by weight of sodium carboxymethyl cellulose, 5 parts by weight of glycerol, and 800 parts by weight of deionized water; D2. Hydroxypropyl methylcellulose and sodium carboxymethyl cellulose were added to deionized water and stirred at 35°C for 4.5 h to obtain a homogeneous polymer solution, wherein the total mass fraction of the polymer was 3.4 wt% of the total mass of the solution, consisting of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose. D3. Add glycerol of this embodiment to the polymer solution obtained in step D2, stir at 35°C for 0.8 h, and degas under reduced pressure for 1.6 h. The reduced pressure in this embodiment is 0.02 MPa absolute pressure, to obtain the film substrate solution of this embodiment; D4. Quality control: The pH of the thin film substrate solution in this embodiment is 6.5.

[0051] Preparation method of the composition: S1. Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder; S2. Preparation of icariin-β-cyclodextrin inclusion complex powder; S3. Prepare a citric acid-trisodium citrate buffer solution; S4. At 35℃, 22 parts by weight of sildenafil citrate-β-cyclodextrin inclusion complex powder and 13.3 parts by weight of icariin-β-cyclodextrin inclusion complex powder were added to the above film substrate solution. 30.0 parts by weight of roasted leek seed powder (passed through a 300-mesh sieve) were added, along with 0.6 parts by weight of polysorbate 80 and 18.7 parts by weight of citrate-trisodium citrate buffer solution. The mixture was stirred for 1.6 hours to obtain the film-forming solution. The film-forming solution of this embodiment was subjected to degassing under reduced pressure. The degassing pressure was 0.02 MPa absolute, and the degassing time was 1.5 h. S5. The film-forming solution obtained in step S4 is cast into a film. In this embodiment, the film-forming is done using a doctor blade with a blade gap of 600 μm. The film is then dried at 55°C for 50 min to obtain a dry film. The dry film thickness in this embodiment is 150 μm. Furthermore, the oral mucosa fast-dissolving film composition in this embodiment does not use gelatin as a film-forming material. The moisture content of the dried film composition in this embodiment is 7.2 wt%. The residual ethanol content of the dried film composition in this embodiment is 4200 ppm. S6. The dry film obtained in step S5 is cut to obtain the oral mucosa fast-dissolving film composition of this embodiment, wherein the dry film of this embodiment is cut into single-piece dosing units and the area of ​​a single-piece dosing unit of this embodiment is 10cm²; In this embodiment, the single-dose unit is packaged in an aluminum-plastic composite package; the packaged film in this embodiment is stored at 25°C.

[0052] In this embodiment, the mass ratio of hydroxypropyl methylcellulose to sodium carboxymethyl cellulose is 1.0:0.56.

[0053] The dissolution (disintegration) time of the oral mucosa rapid-dissolving film in this embodiment was determined by testing in purified water at 37°C, and the dissolution time was 90 seconds.

[0054] Features of Example 2: This example employs a highly active ingredient-loaded formulation, with sildenafil citrate reaching 5.0% and icariin reaching 3.0%, both maximum values ​​within the scope of the claims. Combined with a high solids content of 30.0% roasted leek seed powder, it achieves enhanced overall efficacy and therapeutic strength of the traditional Chinese medicine compound in a single tablet dosage. The total β-cyclodextrin content of 27.3% is achieved through a low inclusion efficiency, ensuring sufficient inclusion and stable protection of the active ingredient. The molar ratio of β-cyclodextrin to the active ingredient is close to the lower limit, optimizing the formation of the inclusion complex. The ratio of 18.0% hydroxypropyl methylcellulose and 10.0% sodium carboxymethyl cellulose provides support for high drug loading while ensuring film-forming properties. The process parameters employ a relatively high temperature (45°C for inclusion reaction, 70°C for drying) and a relatively long time (5 hours for inclusion, 10 hours for drying) to ensure the inclusion reaction proceeds fully. The film thickness of 150 μm, the single-sheet area of ​​10 cm², and the rapid disintegration time of 90 s are designed to meet the release requirements of high drug loading. This embodiment is particularly suitable for applications requiring strong efficacy, and is suitable for male function improvement applications with high therapeutic requirements. It can be stored at room temperature, providing a solution for high-dose clinical needs.

[0055] Example 3 This embodiment provides a combination of traditional Chinese and Western medicine to improve male function, which exists in the form of a fast-dissolving film on the oral mucosa.

[0056] Composition of the composition: Based on the total mass of the solid components in the dry film of the composition of this embodiment, and expressed as a percentage by mass, it includes: 2.0% sildenafil citrate, 1.0% icariin, 50.0% roasted leek seed powder, 11.7% total β-cyclodextrin, 15.0% hydroxypropyl methylcellulose, 12.0% sodium carboxymethyl cellulose, 5.0% glycerol, 1.1% polysorbate 80, 0.77% citric acid, and 1.43% trisodium citrate dihydrate.

[0057] The composition of this embodiment comprises: a sildenafil citrate-β-cyclodextrin inclusion complex powder formed from sildenafil citrate and β-cyclodextrin, an icariin-β-cyclodextrin inclusion complex powder formed from icariin and β-cyclodextrin, a film substrate formed from hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and glycerol, a citrate-trisodium citrate buffer system, and roasted leek seed powder.

[0058] Molar ratio relationship: In this embodiment, the molar ratio of β-cyclodextrin to sildenafil citrate is 1.0:0.57, and the molar ratio of β-cyclodextrin to icariin is 1.0:0.30.

[0059] Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder: A1. Raw material preparation: 150 parts by weight of β-cyclodextrin, 50.2 parts by weight of sildenafil citrate, and 600 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to sildenafil citrate in this embodiment 1.0:0.57; A2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment and stirred at 42°C for 0.7 h; after adding the sildenafil citrate of this embodiment, stirring was continued at 28°C for 1.5 h; A3. Post-processing: The slurry obtained in step A2 was concentrated under reduced pressure (absolute pressure 0.045 MPa); then dried at 35°C for 5 hours to obtain the sildenafil citrate-β-cyclodextrin inclusion complex powder of this embodiment. A4. Endpoint Criteria and Quality Control: The moisture content of the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 4.2 wt%, and the sildenafil citrate content in the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 25 wt%.

[0060] Preparation of icariin-β-cyclodextrin inclusion complex powder: B1. Raw material preparation: 150 parts by weight of β-cyclodextrin, 26.9 parts by weight of icariin, 400 parts by weight of anhydrous ethanol, and 600 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to icariin in this embodiment 1.0:0.30; B2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment and stirred at 42°C for 0.7 h; the icariin of this embodiment was added to the anhydrous ethanol of this embodiment and stirred at 22°C for 0.3 h; the ethanol solution of icariin of this embodiment was added dropwise to the aqueous solution of β-cyclodextrin of this embodiment at a dropping rate of 2 mL / min, and stirring was continued at 28°C for 1.5 h; B3. Post-processing: The mixture obtained in step B2 was subjected to depressurized removal alcohol, with a depressurization pressure of 0.045 MPa absolute pressure; subsequently, it was dried at 35°C for 5 hours to obtain the icariin-β-cyclodextrin inclusion complex powder of this embodiment; B4. Endpoint Criteria and Quality Control: The residual ethanol content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 1500 ppm, the moisture content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 4.2 wt%, and the icariin content in the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 15 wt%.

[0061] Preparation of citric acid-trisodium citrate buffer solution: C1. Raw material preparation: Mix 35 parts by weight of citric acid, 65 parts by weight of trisodium citrate dihydrate, and 1500 parts by weight of deionized water; C2. The citric acid and trisodium citrate dihydrate of this embodiment are dissolved in the deionized water of this embodiment, and stirred at 22°C for 0.3 h to obtain a citric acid-trisodium citrate buffer solution; C3. Endpoint Criteria and Quality Control: The pH of the citric acid-trisodium citrate buffer solution in this embodiment is 5.5.

[0062] Thin film substrate solution preparation: D1. Raw material preparation: Weigh out 15 parts by weight of hydroxypropyl methylcellulose, 12 parts by weight of sodium carboxymethyl cellulose, 5 parts by weight of glycerol, and 1200 parts by weight of deionized water; D2. Hydroxypropyl methylcellulose and sodium carboxymethyl cellulose were added to deionized water and stirred at 22°C for 2.0 h to obtain a homogeneous polymer solution, wherein the total mass fraction of the polymer was 2.2 wt% of the total mass of the solution, consisting of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose. D3. Add glycerol of this embodiment to the polymer solution obtained in step D2, stir at 22°C for 0.3 h, and degas under reduced pressure for 0.6 h. The reduced pressure in this embodiment is an absolute pressure of 0.045 MPa, to obtain the film substrate solution of this embodiment; D4. Quality control: The pH of the thin film substrate solution in this embodiment is 5.5.

[0063] Preparation method of the composition: S1. Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder; S2. Preparation of icariin-β-cyclodextrin inclusion complex powder; S3. Prepare a citric acid-trisodium citrate buffer solution; S4. At 22℃, 8 parts by weight of sildenafil citrate-β-cyclodextrin inclusion complex powder and 6.67 parts by weight of icariin-β-cyclodextrin inclusion complex powder were added to the above film substrate solution. 50.0 parts by weight of roasted leek seed powder (passed through a 300-mesh sieve) were added, along with 1.1 parts by weight of polysorbate 80 and 35.2 parts by weight of citric acid-trisodium citrate buffer solution. The mixture was stirred for 0.6 h to obtain the film-forming solution. The film-forming solution of this embodiment was subjected to degassing under reduced pressure. The degassing pressure was 0.045 MPa (absolute pressure), and the degassing time was 0.3 h. S5. The film-forming solution obtained in step S4 is cast into a film. In this embodiment, the film-forming is done using a doctor blade with a doctor blade gap of 200 μm. The film is then dried at 35°C for 15 min to obtain a dry film. The dry film thickness in this embodiment is 50 μm. Furthermore, the oral mucosa fast-dissolving film composition in this embodiment does not use gelatin as a film-forming material. The moisture content of the dried film composition in this embodiment is 4.5 wt%. The residual ethanol content of the dried film composition in this embodiment is 1500 ppm. S6. The dry film obtained in step S5 is cut to obtain the oral mucosa fast-dissolving film composition of this embodiment, wherein the dry film of this embodiment is cut into single-piece dosing units and the area of ​​a single-piece dosing unit of this embodiment is 3cm²; In this embodiment, the single-dose unit is packaged in an aluminum-plastic composite package; the packaged film in this embodiment is stored at 8°C.

[0064] In this embodiment, the mass ratio of hydroxypropyl methylcellulose to sodium carboxymethyl cellulose is 1.0:0.8.

[0065] The dissolution (disintegration) time of the oral mucosa rapid-dissolving film in this embodiment was determined by measuring it in purified water at 37°C, and the dissolution time was 25 seconds.

[0066] Features of Example 3: This example employs a low-activity-content and high-concentration traditional Chinese medicine powder loading formulation. Sildenafil citrate (2.0%) and icariin (1.0%) are at the lower end of the claims, while roasted leek seed powder (50.0%) is at the upper end, suitable for applications emphasizing the conditioning strength and rapid disintegration and dispersion of traditional Chinese medicine compound formulas. The total β-cyclodextrin content of 11.7% meets the scope requirements, ensuring basic inclusion protection of the active ingredients. The combination of hydroxypropyl methylcellulose (15.0%) and sodium carboxymethyl cellulose (12.0%) provides good film-forming properties and mechanical strength, while glycerol (5.0%) imparts good flexibility and palatability to the film. The high polysorbate 80 content (1.1%) enhances the dispersibility and dissolution rate of the active ingredients. The process parameters employ low-temperature, short-time conditions (inclusion reaction 28°C, drying 35°C, casting drying 15 min) to maximize the stability of the active ingredients and reduce energy consumption. The film's thickness of only 50μm, single-piece area of ​​3cm², and rapid dissolution / disintegration time of 25s enable ultra-fast dissolution and release. The pH 5.5 weakly acidic buffer system closely resembles the oral physiological environment. This embodiment is particularly suitable for applications requiring extremely fast onset of action and rapid absorption. It is suitable for daily health maintenance and gentle conditioning. The small-area single-piece design facilitates portability and careful use. Refrigerated storage is recommended to extend shelf life, providing an ideal choice for users seeking rapid onset of action.

[0067] Example 4 This embodiment provides a combination of traditional Chinese and Western medicine to improve male function, which exists in the form of a fast-dissolving film on the oral mucosa.

[0068] Composition of the composition: Based on the total mass of the solid components in the dry film of the composition of this embodiment, and by mass percentage, it includes: 1.5% sildenafil citrate, 0.8% icariin, 30.0% roasted leek seed powder, 11.7% total β-cyclodextrin, 30.0% hydroxypropyl methylcellulose, 18.0% sodium carboxymethyl cellulose, 5.5% glycerol, 1.5% polysorbate 80, 0.34% citric acid, and 0.66% trisodium citrate dihydrate.

[0069] The composition of this embodiment comprises: a sildenafil citrate-β-cyclodextrin inclusion complex powder formed from sildenafil citrate and β-cyclodextrin, an icariin-β-cyclodextrin inclusion complex powder formed from icariin and β-cyclodextrin, a film substrate formed from hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and glycerol, a citrate-trisodium citrate buffer system, and roasted leek seed powder.

[0070] Molar ratio relationship: In this embodiment, the molar ratio of β-cyclodextrin to sildenafil citrate is 1.0:0.57, and the molar ratio of β-cyclodextrin to icariin is 1.0:0.18.

[0071] Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder: A1. Raw material preparation: 150 parts by weight of β-cyclodextrin, 50.2 parts by weight of sildenafil citrate, and 2800 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to sildenafil citrate in this embodiment 1.0:0.57; A2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment and stirred at 56°C for 1.4 h; after adding the sildenafil citrate of this embodiment, stirring was continued at 48°C for 5.5 h; A3. Post-processing: The slurry obtained in step A2 was concentrated under reduced pressure (absolute pressure 0.015 MPa); then dried at 75°C for 11 h to obtain the sildenafil citrate-β-cyclodextrin inclusion complex powder of this embodiment. A4. Endpoint Criteria and Quality Control: The moisture content of the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 1.5 wt%, and the sildenafil citrate content in the sildenafil citrate-β-cyclodextrin inclusion complex powder in this embodiment is 25 wt%.

[0072] Preparation of icariin-β-cyclodextrin inclusion complex powder: B1. Raw material preparation: 110 parts by weight of β-cyclodextrin, 11.8 parts by weight of icariin, 1900 parts by weight of anhydrous ethanol, and 2800 parts by weight of deionized water were mixed to make the molar ratio of β-cyclodextrin to icariin in this embodiment 1.0:0.18; B2. Inclusion reaction: The β-cyclodextrin of this embodiment was added to the deionized water of this embodiment and stirred at 56°C for 1.4 h; the icariin of this embodiment was added to the anhydrous ethanol of this embodiment and stirred at 38°C for 0.9 h; the ethanol solution of icariin of this embodiment was added dropwise to the aqueous solution of β-cyclodextrin of this embodiment at a dropping rate of 9.5 mL / min, and stirring was continued at 48°C for 5.5 h; B3. Post-processing: The mixture obtained in step B2 was subjected to depressurized removal alcohol, with a depressurization pressure of 0.015 MPa absolute pressure; subsequently, it was dried at 75°C for 11 h to obtain the icariin-β-cyclodextrin inclusion complex powder of this embodiment; B4. Endpoint Criteria and Quality Control: The residual ethanol content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 4700 ppm, the moisture content of the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 1.5 wt%, and the icariin content in the icariin-β-cyclodextrin inclusion complex powder in this embodiment is 10 wt%.

[0073] Preparation of citric acid-trisodium citrate buffer solution: C1. Raw material preparation: Mix 47 parts by weight of citric acid, 93 parts by weight of trisodium citrate dihydrate, and 1850 parts by weight of deionized water; C2. The citric acid and trisodium citrate dihydrate of this embodiment are dissolved in the deionized water of this embodiment, and stirred at 38°C for 0.9 h to obtain a citric acid-trisodium citrate buffer solution; C3. Endpoint Criteria and Quality Control: The pH of the citric acid-trisodium citrate buffer solution in this embodiment is 6.8.

[0074] Thin film substrate solution preparation: D1. Raw material preparation: Weigh out 30 parts by weight of hydroxypropyl methylcellulose, 18 parts by weight of sodium carboxymethyl cellulose, 5.5 parts by weight of glycerol, and 1850 parts by weight of deionized water; D2. Hydroxypropyl methylcellulose and sodium carboxymethyl cellulose were added to deionized water and stirred at 38°C for 5.5 h to obtain a homogeneous polymer solution, wherein the total mass fraction of the polymer was 2.5 wt% of the total mass of the solution, consisting of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose. D3. Add glycerol of this embodiment to the polymer solution obtained in step D2, stir at 38°C for 0.9 h, and degas under reduced pressure for 1.85 h. The reduced pressure in this embodiment is an absolute pressure of 0.015 MPa, to obtain the film substrate solution of this embodiment; D4. Quality control: The pH of the thin film substrate solution in this embodiment is 6.8.

[0075] Preparation method of the composition: S1. Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder; S2. Preparation of icariin-β-cyclodextrin inclusion complex powder; S3. Prepare a citric acid-trisodium citrate buffer solution; S4. At 38℃, 6.0 parts by weight of sildenafil citrate-β-cyclodextrin inclusion complex powder and 8.0 parts by weight of icariin-β-cyclodextrin inclusion complex powder were added to the above film substrate solution, along with 30.0 parts by weight of roasted leek seed powder (passed through a 300-mesh sieve), 1.5 parts by weight of polysorbate 80, and 14.2 parts by weight of citric acid-trisodium citrate buffer solution. The mixture was stirred for 1.85 h to obtain the film-forming solution. The film-forming solution of this embodiment was subjected to degassing under reduced pressure. The degassing pressure was 0.015 MPa absolute, and the degassing time was 1.85 h. S5. The film-forming solution obtained in step S4 is cast into a film. In this embodiment, the film-forming is done using a doctor blade with a blade gap of 740 μm. The film is then dried at 57°C for 55 min to obtain a dry film. The dry film thickness in this embodiment is 185 μm. Furthermore, the oral mucosa fast-dissolving film composition in this embodiment does not use gelatin as a film-forming material. The moisture content of the dried film composition in this embodiment is 7.6 wt%. The residual ethanol content of the dried film composition in this embodiment is 4700 ppm. S6. The dry film obtained in step S5 is cut to obtain the oral mucosa fast-dissolving film composition of this embodiment, wherein the dry film of this embodiment is cut into single-piece dosing units and the area of ​​a single-piece dosing unit of this embodiment is 11 cm²; In this embodiment, the single-dose unit is packaged in an aluminum-plastic composite package; the packaged film in this embodiment is stored at 28°C.

[0076] In this embodiment, the mass ratio of hydroxypropyl methylcellulose to sodium carboxymethyl cellulose is 1.0:0.60.

[0077] The dissolution (disintegration) time of the oral mucosa rapid-dissolving film in this embodiment was determined by testing in purified water at 37°C, and the dissolution time was 110 s.

[0078] Features of Example 4: This example uses a formulation with low active ingredients and a medium film-forming matrix. Sildenafil citrate (1.5%) and icariin (0.8%) are within the lower range of the claims, and roasted leek seed powder (30.0%) is within the lower limit of the claims. This ensures both the loading of the herbal powder and the film-forming properties and mechanical integrity. The total β-cyclodextrin content of 11.7% meets the requirements. In this example, the molar ratio of β-cyclodextrin to sildenafil citrate is 1.0:0.57, and the molar ratio of β-cyclodextrin to icariin is 1.0:0.18, to achieve inclusion, solubilization, and improved stability of the active ingredients. The ratio of hydroxypropyl methylcellulose (30.0%) to sodium carboxymethyl cellulose (18.0%) provides a good balance between film-forming properties and mechanical strength. Glycerin (5.5%) is used to improve film flexibility; polysorbate 80 (1.5%) is used to improve powder wetting and dispersion and film surface uniformity. Citric acid (0.34%) and trisodium citrate dihydrate (0.66%) were used to construct a buffer system with a near-neutral pH of 6.8, contributing to oral comfort and storage stability. The film thickness of 185 μm, single-sheet area of ​​11 cm², and rapid disintegration time of 110 s were designed to meet the drug loading and handling requirements of this system. This embodiment is suitable for applications emphasizing mild conditioning and good physical stability.

[0079] Comparative Example 1: Essentially the same as Example 1, except that the mass percentage of sildenafil citrate in the dry film was adjusted to 0.3% to verify the impact of insufficient sildenafil content on overall performance. To ensure that the total mass percentage "based on the total mass of solid components in the dry film" is 100%, except for the change in the labeled amount of sildenafil citrate, the mass percentages of the other solid components were normalized according to the relative proportions of Example 1. The amount of sildenafil citrate-β-cyclodextrin inclusion complex added was accordingly reduced to meet the target labeled amount.

[0080] Comparative Example 2: Essentially the same as Example 1, except that the mass percentage of sildenafil citrate in the dry film was adjusted to 5.5% to verify the effect of ultra-high sildenafil loading on film uniformity, mechanical properties, and rapid solubility. To ensure that the total mass percentage "based on the total mass of solid components in the dry film" is 100%, except for the change in the labeled amount of sildenafil citrate, the mass percentages of the other solid components were normalized according to the relative proportions of Example 1. The amount of sildenafil citrate-β-cyclodextrin inclusion complex added was accordingly increased to meet the target labeled amount.

[0081] Comparative Example 3: Essentially the same as Example 1, except that the mass percentage of icariin in the dry film was adjusted to 0.05% to verify the effect of insufficient icariin content on synergistic effects and overall performance. To ensure that the total mass percentage "based on the total mass of solid components in the dry film" is 100%, except for the change in the labeled amount of icariin, the mass percentages of the other solid components were normalized according to the relative proportions of Example 1. The amount of icariin-β-cyclodextrin inclusion complex added was accordingly reduced to meet the target labeled amount.

[0082] Comparative Example 4: Basically the same as Example 1, except that: the total β-cyclodextrin content in the dry film was adjusted to 8% to construct a "insufficient inclusion carrier" scenario and to examine its effect on encapsulation efficiency, dispersion stability, content uniformity, and film quality; to keep the labeled amounts of sildenafil citrate and icariin constant at 3.0% and 2.0% respectively, without changing the other excipient system and the same preparation process conditions, the amount of β-cyclodextrin used to form the two inclusion complexes was reduced accordingly, so that there are more unencapsulated free active ingredients in the system; and to ensure that the total mass percentage "based on the total mass of solid components in the dry film" is 100%, the mass percentage of the other solid components except "total β-cyclodextrin" was normalized according to the relative proportions of Example 1.

[0083] Comparative Example 5: Basically the same as Example 1, except that inclusion technology was not used. Sildenafil 20 parts by mass 3.0 parts by mass, icariin 2.0 parts by mass and β-cyclodextrin 17.0 parts by mass were directly added to the film substrate solution and mixed. Roasted leek seed powder (same amount as in Example 1) was added. The inclusion reaction steps (A2 and B2) and the vacuum concentration / dealcoholization steps (A3 and B3) were omitted. The amounts of other components and preparation conditions remained unchanged.

[0084] Comparative Example 6: Basically the same as Example 1, except that the mass ratio of hydroxypropyl methylcellulose to sodium carboxymethyl cellulose was adjusted to 1.0:3.0 to verify the effect of the imbalance of the dual polymer synergistic film-forming system on the mechanical integrity and rapid solubility of the film; the remaining components were still formulated at the same level as in Example 1 (sildenafil citrate 3.0%, icariin 2.0%, roasted leek seed powder 40.0%, total β-cyclodextrin 17.0%, glycerol 6.0%, polysorbate 800.8%, citric acid 0.4%, trisodium citrate dihydrate 0.8%) and the same preparation process conditions remained unchanged.

[0085] Comparative Example 7: Basically the same as Example 1, except that the reaction temperature of inclusion reaction steps A2 and B2 was reduced to 15°C to construct a "low-temperature insufficient inclusion" situation and evaluate its effect on encapsulation efficiency, dispersion stability, content uniformity and film overall performance; the formulation of other components (sildenafil citrate 3.0%, icariin 2.0%, roasted leek seed powder 40.0%, total β-cyclodextrin 17.0%, HPMC 18.0%, CMC-Na 12.0%, glycerol 6.0%, polysorbate 80 0.8%, citric acid 0.4%, trisodium citrate dihydrate 0.8%) and subsequent casting, drying, cutting and packaging processes were the same as in Example 1.

[0086] Comparative Example 8: Basically the same as Example 1, except that the citric acid-trisodium citrate buffer system was not added: citric acid (0.4% based on dry film solids) and trisodium citrate dihydrate (0.8% based on dry film solids) were omitted, and the film-forming solution ratio was adjusted with deionized water to maintain a consistent solid content in the film-forming solution; at the same time, to ensure that the total mass percentage of dry film solids is 100%, the above-mentioned 1.2% solids difference was made up with hydroxypropyl methylcellulose, and the formulation and preparation conditions of the remaining components were the same as in Example 1.

[0087] Performance testing: Determination of rapid disintegration time Test Subject: Single-dose unit of oral mucosal fast-dissolving film composition. Test Objective: To evaluate the rapid wetting, dissolving, and releasing performance of the film in a simulated oral environment. Test Principle: The film achieves rapid dissolution (disintegration) in purified water at 37℃ through rapid swelling and disintegration of the hydrophilic film-forming matrix, rapid dispersion and dissolution of the inclusion complex, and wetting and dispersion by roasted leek seed powder. The dissolution time reflects the film's wetting properties and the synergistic release characteristics of the film-forming matrix. Experimental Method: A single-dose unit was placed in a beaker containing 100mL of purified water at 37℃±0.5℃. The mixture was gently stirred, and the time for the film matrix to completely disintegrate and form a uniform dispersion system was recorded. The endpoint was defined as the absence of visible whole tablets or large clumps. Key Parameters: Test temperature 37±0.5℃, water volume 100mL, stirring speed 50rpm. Data Processing: Six tablets were tested in parallel, and the mean ± standard deviation (n=6) was used. The rapid dissolution time should be ≤120s.

[0088] Determination of tensile strength and elongation at break Test Subject: Dry film of oral mucosal fast-dissolving film composition. Test Objective: To evaluate the mechanical integrity and flexibility of the film, and to verify the mechanical strength of the synergistic film-forming system of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose. Test Principle: The film deforms under external force until it breaks. Tensile strength reflects the film's ability to withstand tensile loads, while elongation at break reflects the film's flexibility and resistance to brittleness. Experimental Method: The dry film was cut into strips 50 mm long and 15 mm wide. Using a texture analyzer or universal testing machine, the test was conducted at a tensile rate of 50 mm / min under conditions of 25 ± 2℃ and 45 ± 5% relative humidity. The maximum tensile force and elongation at break were recorded. Key Parameters: Initial clamp spacing 30 mm, tensile rate 50 mm / min, temperature 25 ± 2℃, humidity 45 ± 5%. Data processing: Tensile strength (MPa) = maximum tensile force / cross-sectional area; Elongation at break (%) = (gauge length at break - original gauge length) / original gauge length × 100%; Six parallel specimens were measured, and the mean ± standard deviation was taken (n=6).

[0089] Encapsulation efficiency determination Test Subjects: Sildenafil citrate-β-cyclodextrin inclusion complex powder and icariin-β-cyclodextrin inclusion complex powder. Test Objective: To quantitatively evaluate the inclusion efficiency of β-cyclodextrin for the active ingredient and verify the structure retention ability of the inclusion complex. Test Principle: By measuring the difference in content of free active ingredient and total active ingredient before and after inclusion, the encapsulation efficiency is calculated to reflect the effectiveness of the host-guest inclusion effect. Experimental Method: An appropriate amount of inclusion complex powder was accurately weighed, and the total active ingredient was extracted with methanol using ultrasound. An equal amount of powder was dissolved in purified water, filtered through a 0.45 μm filter membrane, and the free active ingredient was measured. The content of the active ingredient was determined using high-performance liquid chromatography (HPLC) under the following chromatographic conditions: C18 column, mobile phase acetonitrile-phosphate buffer (gradient elution), and detection wavelength of 292 nm (sildenafil) or 270 nm (icariin). Key parameters: ultrasonic power 250W, ultrasonic time 30min, column temperature 30℃, flow rate 1.0mL / min. Data processing: Encapsulation efficiency (%) = (total content - free content) / total content × 100%; parallel determinations were performed in triplicate, and the mean ± standard deviation was taken (n=3).

[0090] Content uniformity determination Test Subject: Single-dose units of oral mucosal fast-dissolving film composition. Test Objective: To evaluate the uniformity of active ingredient distribution in the film and verify the uniformity and stability of the coating process. Test Principle: By measuring the content of active ingredient in single units at different locations, the relative standard deviation (RSD) is calculated to reflect the influence of solid content distribution and defoaming effect of the film-forming solution on content uniformity. Experimental Method: Ten single-dose units were randomly selected and placed in volumetric flasks. Methanol was added, and the solution was diluted to volume. After filtration through a 0.45 μm filter membrane, the contents of sildenafil citrate and icariin were determined by HPLC under the same chromatographic conditions as in Experiment 3. Key Parameters: Single-unit integrity confirmation; dissolution time ≤ 10 min; chromatographic conditions as in the encapsulation rate determination. Data Processing: Content uniformity (%) = Single-unit content / Labeled amount × 100%; Calculate the mean, standard deviation, and RSD of the 10 units (n=10), requiring RSD ≤ 5.0%.

[0091] Determination of moisture and residual solvent Test Subject: Dry film of oral mucosal fast-dissolving film composition. Test Objective: To evaluate the low moisture and low residual solvent storage stability of the film and verify the effectiveness of the drying process. Test Principle: Moisture content was determined using the Karl Fischer method, based on the quantitative reaction of water with iodine and sulfur dioxide; residual ethanol was determined using headspace gas chromatography, quantifying the ethanol concentration in the gas phase after gas-liquid equilibrium. Experimental Methods: Moisture determination: Weigh 0.1-0.5 g of the film and automatically titrate in a Karl Fischer titration cell; Residual ethanol determination: Weigh 0.1 g of the film and dissolve it in 5 mL of dimethyl sulfoxide, equilibrate at 80℃ for 30 min, and then inject for GC determination. Chromatographic conditions: DB-624 column, FID detector, column temperature 60℃, detector temperature 250℃. Standard Basis: Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0832 Moisture Determination Method and 0861 Residual Solvent Determination Method. Key Parameters: Karl Fischer sensitivity 0.001 mg; GC injection volume 1 mL, split ratio 10:1, carrier gas flow rate 2 mL / min. Data processing: Moisture (%) = titration volume of water / sample mass × 100%; perform three parallel determinations and take the average value ± standard deviation (n=3). Moisture content ≤ 8.0% and ethanol content ≤ 5000 ppm are required.

[0092] X-ray diffraction characterization Test Subjects: Sildenafil citrate-β-cyclodextrin inclusion complex powder, icariin-β-cyclodextrin inclusion complex powder, pure active ingredient, and pure β-cyclodextrin reference standard. Test Objective: To demonstrate the formation of the inclusion complex through changes in crystal phase structure and to verify the effect of inclusion on the crystalline state of the active ingredient. Test Principle: Inclusion causes the active ingredient to enter the β-cyclodextrin cavity, resulting in a change in crystal form or a transformation into an amorphous state. Changes in the position and intensity of characteristic peaks in the XRD pattern can prove the formation of the host-guest inclusion complex. Experimental Method: Take appropriate amounts of each sample, place them flat on the sample stage, and measure using an X-ray diffractometer. The scanning range is 5-60° (2θ), the step size is 0.02°, the scanning rate is 5° / min, the radiation source is CuKα (λ=0.15406nm), the tube voltage is 40kV, and the tube current is 40mA. Key Parameters: Scanning range 5-60°, step size 0.02°, scanning rate 5° / min, radiation source CuKα. Data processing: Compare the diffraction patterns of the inclusion compound and the pure product, analyze the disappearance, shift or appearance of characteristic peaks to determine the formation of the inclusion compound; export CSV format data (2θ, Intensity) for Origin plotting and comparison.

[0093] Figure 1 The XRPD patterns are from X-ray powder diffraction, with the samples being Example 1 and Comparative Example 5. The characterization method was X-ray powder diffraction testing. Fixed parameters were: CuKα radiation source, tube voltage 40 kV, tube current 40 mA, scanning range 5–60°2θ, step size 0.02°, and scanning rate 5°·min⁻¹. The parameter change was that the sample preparation method was changed from the inclusion complex system of Example 1 to the direct physical mixing system of Comparative Example 5. In Example 1, the sharp characteristic diffraction peaks related to the active ingredient were significantly weakened or disappeared, and the spectrum tended to be broad and diffuse. In contrast, Comparative Example 5 retained more sharp crystalline peaks, indicating that the inclusion treatment promoted the transformation of the active ingredient from a clearly crystalline state to an amorphous or new host-guest phase structure, thus verifying the correctness of the inclusion complex formation and crystal state regulation.

[0094] Figure 2 The Fourier transform infrared (FTIR) spectra are those of Example 1 and Comparative Example 5, characterized by FTIR spectroscopy. Fixed parameters included a spectral scanning range of 4000–400 cm⁻¹ and the same spectral normalization method. The variable parameter was the sample preparation method, changing the inclusion complex system of Example 1 to a physical mixture system of Comparative Example 5. In Example 1, the characteristic vibrational peaks of the active ingredient showed identifiable shifts and intensity changes in peak position and shape, with some characteristic peak boundaries becoming blunt and shoulder peaks weakening. Comparative Example 5, on the other hand, showed more of a simple superposition of peak shapes from each component, indicating stronger intermolecular interactions and hydrogen bond network rearrangement in Example 1, supporting enhanced host-guest interactions consistent with the formation of the inclusion structure.

[0095] Figure 3 The particle size probability density distribution is shown in the dynamic light scattering diagrams, with examples 1 and 4. The characterization method is dynamic light scattering particle size distribution testing. Fixed parameters include displaying the particle size range on logarithmic coordinates, expressing the distribution as a continuous probability density curve, and maintaining consistent calculation calibers. The variable parameter is the inclusion carrier level, changing from the β-cyclodextrin-sufficient condition in Example 1 to the β-cyclodextrin-deficient condition in Comparative Example 4. Example 1 shows a more concentrated particle size distribution and a lower contribution from the large particle tail, indicating more stable particle dispersion and suppressed agglomeration. Comparative Example 4 shows a significantly broadened distribution and enhanced contribution from the large particle size region, reflecting that insufficient inclusion leads to an increase in free components and aggregates, thus verifying that sufficient inclusion carrier can improve dispersion uniformity and support the conclusion of film uniformity.

[0096] Figure 4 The cumulative particle size distribution is plotted for dynamic light scattering, using the examples of Example 1 and Comparative Example 4. The characterization method is dynamic light scattering cumulative distribution analysis. Fixed parameters include a monotonically increasing cumulative distribution curve, logarithmic coordinates for particle size, and the calculation of D10, D50, and D90 using the same algorithm. The variable parameter is the β-cyclodextrin level, which changes from the sufficient condition in Example 1 to the insufficient condition in Comparative Example 4. The cumulative curve of Example 1 reaches the 50% and 90% cumulative values ​​more quickly at smaller particle sizes, indicating that D50 and D90 are smaller and have a narrower distribution. The cumulative curve of Comparative Example 4 shifts to the right overall, and the 90% point corresponds to a larger particle size, indicating the presence of more large particles and agglomeration in the system, quantitatively supporting the correctness of inclusion solubilization and improved dispersion stability.

[0097] Figure 5 The N1s binding energy spectra are obtained from X-ray photoelectron spectroscopy, with the formats of Example 1 and Comparative Example 8. Characterization was performed using XPS high-resolution N1s measurements. Fixed parameters included the same energy step and testing conditions, consistent spectral normalization and background processing, and binding energy as the abscissa. The variable parameter was the system environment, changing from the citrate-trisodium citrate buffer system of Example 1 to the unbuffered system of Comparative Example 8. Example 1 and Comparative Example 8 showed differences in peak position and peak shape ratio in the N1s region, reflecting changes in the surface nitrogen-related chemical states and protonation environment. This indicates that the buffer environment can regulate the interfacial chemical microenvironment and help maintain a more stable intermolecular interaction state, thus supporting the assessment of the stabilizing effect of the buffer system.

[0098] Figure 6The O1s binding energy spectra are obtained from X-ray photoelectron spectroscopy, with the same formats as Example 1 and Comparative Example 8. Characterization was performed using XPS high-resolution O1s testing. Fixed parameters included the same binding energy scanning range and resolution, and the same normalization and background processing methods. The variable parameter was the system environment, changing from the citrate-trisodium citrate buffer system of Example 1 to the unbuffered system of Comparative Example 8. The peak shape and relative intensity distribution in the O1s region of Example 1 differed identibly from those of Comparative Example 8, reflecting changes in the hydrogen bond network and local chemical environment of oxygen-related functional groups. This indicates that the buffer system can stabilize interfacial interactions at the surface level and reduce chemical state drift caused by environmental fluctuations, further demonstrating the supporting role of the buffer system in maintaining structure and interface stability.

[0099] As can be seen from the performance of the examples and comparative examples in Table 1, Examples 1-4 all exhibit excellent overall performance balance. Example 1 achieves the best balance in terms of rapid dissolution time, mechanical strength, encapsulation efficiency, content uniformity, and storage stability. The rapid dissolution time of 60s meets the requirement for rapid onset of action, the tensile strength of 4.2MPa ensures film integrity, the encapsulation efficiency exceeding 78% ensures stable protection of the active ingredient, and the content uniformity RSD of only 2.5% reflects the high uniformity of the coating film-forming process. Moisture and ethanol residues are both well controlled. Example 3 achieves ultra-fast dissolution (25s) and ultra-high mechanical strength (5.8MPa) by increasing the proportion of the film-forming matrix, making it suitable for applications with extremely high requirements for onset of action. Examples 2 and 4 maintain good performance even under high drug loading. In contrast, Comparative Example 2, due to sildenafil exceeding its range, experienced a significantly prolonged disintegration time to 135 s, a decrease in mechanical strength to 2.8 MPa, and a deterioration in content uniformity to an RSD of 6.5%, reflecting that the high drug load exceeded the system's carrying capacity, resulting in a significant narrowing of the coating film uniformity and defoaming processing window. Comparative Example 4, due to insufficient β-cyclodextrin, saw a sharp drop in encapsulation efficiency to below 52% and a deterioration in content uniformity RSD to 8.2%, demonstrating that insufficient inclusion carriers cannot effectively protect the structure of the active ingredient. Comparative Example 5, due to the lack of inclusion technology, experienced a prolonged disintegration time to 180 s, a mechanical strength of only 2.2 MPa, an encapsulation efficiency of only 15%, and a content uniformity RSD as high as 1. 2.5%, demonstrating the crucial role of the inclusion complex in rapid dissolution, film quality, and content uniformity; Comparative Example 6, due to an imbalance in the film-forming matrix ratio, resulted in a rapid dissolution disintegration time of 145s, a mechanical strength of only 1.8MPa, and an elongation at break of only 15%, reflecting a significant decrease in the mechanical integrity and flexibility of the film caused by the imbalance of the synergistic film-forming system of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose; Comparative Example 7, due to an excessively low inclusion reaction temperature, resulted in an encapsulation efficiency below 58% and an increase in the content uniformity RSD to 5.8%, demonstrating the importance of the inclusion reaction temperature for inclusion efficiency and structure maintenance; Comparative Example 8, due to the lack of a buffer system, had a relatively small impact on rapid dissolution and mechanical properties, but was still lower than the level of Example 1.

[0100] Table 1 Performance Comparison Summary Table Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that any equivalent structural transformations made under the concept of the present invention and using the contents of the specification and drawings of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. A combination of traditional Chinese and Western medicine for improving male sexual function, characterized in that, Based on the total mass of the solid components in the dry film of the composition, and expressed as a percentage by mass, it comprises: (a) Sildenafil citrate 0.5–5.0%; (b) Icariin 0.1–3.0%; (c) Total β-cyclodextrin 10–40%; wherein the total β-cyclodextrin includes β-cyclodextrin for forming sildenafil citrate-β-cyclodextrin inclusion complex and β-cyclodextrin for forming icariin-β-cyclodextrin inclusion complex. (d) Hydroxypropyl methylcellulose 10–60%; (e) Sodium carboxymethyl cellulose 5–40%; (f) Glycerin 5–25%; (g) Polysorbate 80 0.05–2.0%; (h) Citric acid 0.05–3.0%; (i) Trisodium citrate dihydrate 0.05–3.0%; (j) 30–50% roasted leek seed powder; The composition comprises: a sildenafil citrate-β-cyclodextrin inclusion complex powder formed from sildenafil citrate and β-cyclodextrin, an icariin-β-cyclodextrin inclusion complex powder formed from icariin and β-cyclodextrin, a film substrate formed from hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and glycerol, a citrate-trisodium citrate buffer system, and roasted leek seed powder.

2. The composition according to claim 1, characterized in that, In the sildenafil citrate-β-cyclodextrin inclusion complex, the molar ratio of β-cyclodextrin to sildenafil citrate is 1.0:(0.5-1.2), and in the icariin-β-cyclodextrin inclusion complex, the molar ratio of β-cyclodextrin to icariin is 1.0:(0.1–1.2).

3. The composition according to claim 1, characterized in that, The sildenafil citrate-β-cyclodextrin inclusion complex powder was prepared by the following steps: A1. Raw material preparation: Mix 100–300 parts by weight of β-cyclodextrin, 50–250 parts by weight of sildenafil citrate, and 300–3000 parts by weight of deionized water to make the molar ratio of β-cyclodextrin to sildenafil citrate 1.0:(0.5–1.2); A2. Inclusion reaction: The β-cyclodextrin was added to the deionized water and stirred at 40–60°C for 0.5–1.5 h; after adding the sildenafil citrate, stirring was continued at 25–50°C for 1–6 h. A3. Post-processing: The slurry obtained in step A2 is concentrated under reduced pressure at an absolute pressure of 0.01–0.05 MPa; then dried at 30–80 °C for 4–12 h to obtain the sildenafil citrate-β-cyclodextrin inclusion complex powder. A4. Endpoint Criteria and Quality Control: The moisture content of the sildenafil citrate-β-cyclodextrin inclusion complex powder is ≤5.0wt%, and the sildenafil citrate content in the sildenafil citrate-β-cyclodextrin inclusion complex powder is 20–50wt%.

4. The composition according to claim 1, characterized in that, The icariin-β-cyclodextrin inclusion complex powder was prepared by the following steps: B1. Raw material preparation: Mix 100–400 parts by weight of β-cyclodextrin, 10–200 parts by weight of icariin, 100–2000 parts by weight of anhydrous ethanol and 300–3000 parts by weight of deionized water, so that the molar ratio of β-cyclodextrin to icariin is 1.0:(0.1–1.2); B2. Inclusion reaction: The β-cyclodextrin was added to the deionized water and stirred at 40–60°C for 0.5–1.5 h; the icariin was added to the anhydrous ethanol and stirred at 20–40°C for 0.2–1.0 h; the ethanol solution of the icariin was added dropwise to the aqueous solution of the β-cyclodextrin at a dropping rate of 0.5–10 mL / min and stirred at 25–50°C for 1–6 h. B3. Post-processing: The mixture obtained in step B2 was subjected to de-alcoholization under reduced pressure of 0.01–0.05 MPa absolute pressure; then dried at 30–80 °C for 4–12 h to obtain icariin-β-cyclodextrin inclusion complex powder. B4. Endpoint Criteria and Quality Control: The residual ethanol content of the icariin-β-cyclodextrin inclusion complex powder is ≤5000ppm, the moisture content of the icariin-β-cyclodextrin inclusion complex powder is ≤5.0wt%, and the icariin content in the icariin-β-cyclodextrin inclusion complex powder is 5–30wt%.

5. The composition according to claim 1, characterized in that, The citric acid-trisodium citrate buffer solution is prepared by the following steps: C1. Raw material preparation: Mix 1–50 parts by weight of citric acid, 1–100 parts by weight of trisodium citrate dihydrate, and 100–2000 parts by weight of deionized water; C2. Dissolve the citric acid and the trisodium citrate dihydrate in the deionized water and stir at 20–40°C for 0.2–1.0 h to obtain a citric acid-trisodium citrate buffer solution; C3. Endpoint Criteria and Quality Control: The pH of the citric acid-trisodium citrate buffer solution is 5.0–7.

0.

6. The composition according to claim 1, characterized in that, The thin film substrate solution of the composition is prepared by the following steps: D1. Raw material preparation: Weigh 10–60 parts by weight of hydroxypropyl methylcellulose, 5–40 parts by weight of sodium carboxymethyl cellulose, 5–25 parts by weight of glycerol and 300–2000 parts by weight of deionized water. D2. Hydroxypropyl methylcellulose and sodium carboxymethyl cellulose are added to deionized water and stirred at 20–40°C for 1–6 h to obtain a homogeneous polymer solution, wherein the total mass fraction of the polymer is 2–10 wt% of the total mass of the solution, based on the combined mass of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose. D3. Add the glycerol to the polymer solution obtained in step D2, stir at 20–40°C for 0.2–1.0 h, and degas under reduced pressure for 0.5–2.0 h, wherein the reduced pressure is an absolute pressure of 0.01–0.05 MPa, to obtain the film substrate solution; D4. Quality control: The pH of the thin film substrate solution is 5.0–7.

0.

7. The composition according to claim 1, characterized in that, The dry film thickness of the composition is 30–200 μm, the film composition is cut into single-piece dosing units with an area of ​​2–12 cm², and the oral mucosa fast-dissolving film composition does not use gelatin as a film-forming material. The disintegration time of the oral mucosa rapid-dissolving film was determined by testing in purified water at 37°C, and the disintegration time was 10–120 s.

8. A method for a combination of traditional Chinese and Western medicine for improving male function as described in any one of claims 1-7, characterized in that, Includes the following steps: S1. Preparation of sildenafil citrate-β-cyclodextrin inclusion complex powder; S2. Preparation of icariin-β-cyclodextrin inclusion complex powder; S3. Prepare a citric acid-trisodium citrate buffer solution; S4. At 20–40°C, sildenafil citrate-β-cyclodextrin inclusion complex powder and icariin-β-cyclodextrin inclusion complex powder are added to a film substrate solution, along with polysorbate 80, roasted leek seed powder, and a citrate-trisodium citrate buffer solution. The amounts of the sildenafil citrate-β-cyclodextrin inclusion complex powder added are 0.5–5.0 parts by weight (calculated as sildenafil citrate), 0.1–3.0 parts by weight (calculated as icariin), 30–50 parts by weight of roasted leek seed powder, 0.05–2.0 parts by weight of polysorbate 80, and 5–50 parts by weight of the citrate-trisodium citrate buffer solution. The mixture is stirred for 0.5–2.0 h to obtain a film-forming solution. S5. The film-forming solution obtained in step S4 is cast into a film using a doctor blade with a gap of 100–800 μm; then dried at 30–60°C for 10–60 min to obtain a dry film, wherein the thickness of the dry film is 30–200 μm, and the oral mucosa fast-dissolving film composition does not use gelatin as a film-forming material. S6. Cut the dry film obtained in step S5 to obtain the oral mucosa fast-dissolving film composition, wherein the dry film is cut into single-piece dosing units and the area of ​​the single-piece dosing unit is 2–12 cm². The mass ratio of hydroxypropyl methylcellulose to sodium carboxymethyl cellulose is 1.0:0.2–2.

0.

9. The method according to claim 8, characterized in that, After step S4, the film-forming solution is subjected to degassing under reduced pressure. The degassing pressure is 0.01–0.05 MPa absolute pressure, and the degassing time is 0.2–2.0 h. In step S5, the moisture content of the dried film composition is ≤8.0 wt%; and the residual ethanol content of the dried film composition in step S5 is ≤5000 ppm.

10. The method according to claim 8, characterized in that, The single-piece dosing unit described in step S6 is packaged in an aluminum-plastic composite package; The encapsulated film is stored at 2–30°C.

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