Production process and formula for treating body nodules

Abstract

The invention relates to the technical field of pharmaceutical preparations, and discloses a production process for treating body nodules, which comprises the following steps: S1, extracting and purifying active pharmaceutical ingredients, and preparing liposome quercetin, genistein and sodium hyaluronate; s2, preparing a functional carrier material, namely preparing polyunsaturated phosphatidylcholine and phosphatidylcholine nanoparticles by an emulsification-solvent evaporation method; the invention also discloses a formula for treating body nodules, and the formula comprises the following components in percentage by weight: 15-25% of active pharmaceutical ingredients; 65%-80% of a functional carrier material; 0.2%-1% of an auxiliary reinforcing material; and 5%-10% of a slow release regulator. Precise delivery and controlled release are realized through a multi-responsive nano-carrier, a multi-mode treatment system combining a photothermal effect and magnetic targeting is adopted, the drug targeting and the treatment efficiency are remarkably improved, the drug effect time is prolonged through a slow-release regulator, the drug use frequency is reduced, and the patient compliance is improved.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a production process and a formula for treating body nodules. Background Art

[0002] The treatment of body nodular diseases has always been a focus and difficulty in clinical medicine and drug development. With the deepening of research, traditional treatment methods have gradually exposed their limitations. Surgical resection, as a direct treatment method, although effective, is very traumatic to patients and is difficult to meet the treatment needs of certain benign or chronic nodules. In contrast, drug therapy has become an important choice due to its non-invasive advantages. However, existing drug delivery systems face many technical bottlenecks in the treatment of nodular lesions.

[0003] Current drug treatments are mainly direct injections or topical applications, and their release pattern is usually a rapid diffusion type. This type of preparation releases drugs rapidly in a short period of time. Although it can quickly increase the drug concentration at the lesion site in the early stage, the concentration will then drop rapidly. This release pattern results in a shorter duration of drug action at the lesion site, making it difficult to achieve a sustained therapeutic effect. In addition, rapidly released drugs tend to diffuse in healthy tissues, increasing the risk of unnecessary side effects. Therefore, precise control of drug release time and the duration of action have become important goals in the development of drug preparations.

[0004] In terms of drug delivery, existing technical solutions generally lack targeted design for lesion sites. Nodular lesions are small in size and the surrounding tissues are complex. It is difficult for traditional preparations to achieve centralized distribution of drugs. During the diffusion process, the drugs often deviate from the lesion area, resulting in reduced treatment efficiency. At the same time, the microenvironment of nodular tissue (such as mild acidity or local temperature changes) is not fully utilized, and the drug release process lacks a response mechanism to these environmental changes. This further exacerbates the problem of nonspecific distribution of drugs at the lesion site and affects the treatment effect. Summary of the invention

[0005] In view of the deficiencies of the prior art, the present invention provides a production process and formula for treating body nodules, which solves the problems of short release time, insufficient targeting and inability to respond to the nodule microenvironment of existing drugs in the treatment of body nodular diseases.

[0006] To achieve the above objectives, the present invention is implemented by the following technical scheme: A formulation for treating body nodules, comprising the following components by weight percentage: Active pharmaceutical ingredients: 15%-25%; Functional carrier material: 65%-80%; Auxiliary reinforcement materials: 0.2%-1%; Sustained-release modifier: 5%-10%; in: The active pharmaceutical ingredients include liposomal quercetin, genistein, and sodium hyaluronate; The functional carrier material includes polyunsaturated phosphatidylcholine, chitosan, poly(N-isopropylacrylamide) and phosphatidylcholine; The auxiliary reinforcement material includes iron oxide nanoparticles and carbon dot nanoparticles; The sustained-release regulator includes glycerin and vitamin E acetate.

[0007] Preferably, the liposomal quercetin accounts for 20%-40% of the total weight of the active pharmaceutical ingredients, genistein accounts for 15%-30% of the total weight of the active pharmaceutical ingredients, and sodium hyaluronate accounts for 5%-10% of the total weight of the active pharmaceutical ingredients.

[0008] Preferably, the polyunsaturated phospholipid choline accounts for 30%-45% of the total weight of the functional carrier material, chitosan accounts for 20%-35% of the total weight of the functional carrier material, poly(N-isopropylacrylamide) accounts for 25%-35% of the total weight of the functional carrier material, and phosphatidylcholine accounts for 10%-20% of the total weight of the functional carrier material.

[0009] Preferably, the iron oxide nanoparticles account for 30%-50% of the total weight of the auxiliary reinforcement material, and the carbon dot nanoparticles account for 50%-70% of the total weight of the auxiliary reinforcement material.

[0010] Preferably, the glycerol accounts for 40%-60% of the total weight of the sustained-release regulator, and the vitamin E acetate accounts for 40%-60% of the total weight of the sustained-release regulator.

[0011] A production process for treating body nodules, which is produced based on the above-mentioned formula for treating body nodules, comprises the following steps: S1, extracting and purifying active pharmaceutical ingredients, preparing liposomal quercetin, genistein and sodium hyaluronate; S2. preparing functional carrier materials, including preparing polyunsaturated phosphatidylcholine and phosphatidylcholine nanoparticles by emulsification-solvent evaporation method, and chitosan modification; S3, loading active pharmaceutical ingredients into functional carriers through self-assembly; S4. The functional carrier material is mixed with the active drug, and the mixture is freeze-dried or spray-dried to prepare powder or microparticles.

[0012] Preferably, the specific steps of extracting and purifying the active pharmaceutical ingredient in step S1 are as follows: S1.1. Preparation of liposome quercetin: Quercetin was loaded by supercritical CO2 method, and the extraction conditions included: pressure 25-30MPa, temperature 40-55°C, and extraction time 3-4h; S1.2. Genistein is extracted by ultrasound-assisted extraction. The extraction conditions include: ultrasonic power 250-300W, extraction temperature 50-60℃, extraction time 1.5-2h. The purity of the purified genistein is ≥95%.

[0013] Preferably, the specific preparation conditions of step S2 include: Oil-water ratio: 1:2-1:3; Ultrasonic power: 250-300W; Ultrasonication time: 3-5min; Solvent evaporation conditions: stirring speed 500-800 rpm, time 2-3 h; The chitosan modification is performed by an electrostatic adsorption method, and the modification conditions include: chitosan concentration of 15%-25%, stirring speed of 300-600 rpm, and stirring time of 30-60 min.

[0014] Preferably, the self-assembly conditions in step S4 include: Active drug concentration: 15%-25%; Self-assembly temperature: 25-30℃; Self-assembly pH: 6.5-7.0; Self-assembly stirring speed: 300-600rpm; Self-assembly time: 30-60min.

[0015] Preferably, the drying conditions for preparing the powder or particles in step S4 include: Freeze drying conditions: freezing temperature -40 to -60°C, drying time 12-24h; Spray drying conditions: feed temperature 100-120°C, drying time 30-60min.

[0016] The present invention provides a production process and formula for treating body nodules, which has the following beneficial effects: 1. The present invention adopts a formula design of multi-responsive nanocarriers combined with active drugs, and realizes precise delivery and controlled release of drugs in nodular lesions through pH, ​​temperature and magnetic triggering mechanisms. This technical solution significantly improves the targeting and therapeutic efficiency of drugs. Compared with the technical solutions in the prior art where drug release is not affected by the environment and has poor targeting, it effectively solves the technical defects of premature release of drugs in healthy tissues and low drug utilization.

[0017] 2. The present invention introduces auxiliary reinforcement materials, and forms a multi-modal treatment system through the photothermal effect and magnetic targeting properties of iron oxide and carbon dot nanoparticles. This scheme achieves non-invasive thermal therapy assistance while increasing drug concentration. Compared with the single therapy that only relies on chemical components in the prior art, it overcomes the problems of insufficient local efficacy and single treatment method, and significantly enhances the degradation efficiency of nodule tissue.

[0018] 3. The present invention combines the reasonable ratio design of sustained-release regulators and functional carrier materials, and realizes the long-acting sustained-release function of the drug by regulating the diffusion rate through glycerol and enhancing the stability through vitamin E acetate. Compared with the technical solutions in the prior art with short drug efficacy maintenance time and frequent medication, the present invention effectively solves the problems of rapid drug metabolism and insufficient action time, while reducing the frequency of medication for patients and improving treatment compliance. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a flow chart of the production process of the present invention. DETAILED DESCRIPTION

[0020] The following will be combined with the drawings in the specification of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0021] Please refer to the attached Figure 1 The embodiment of the present invention provides a production process for treating body nodules, which comprises the following components by weight percentage: Active pharmaceutical ingredients: 15%-25%; Functional carrier material: 65%-80%; Auxiliary reinforcement materials: 0.2%-1%; Sustained-release modifier: 5%-10%; in: Active pharmaceutical ingredients include liposomal quercetin, genistein, and sodium hyaluronate; Functional carrier materials include polyunsaturated phospholipid choline, chitosan, poly (N-isopropylacrylamide) and phosphatidylcholine; The auxiliary reinforcement materials include iron oxide nanoparticles and carbon dot nanoparticles; Sustained-release modifiers include glycerin and vitamin E acetate.

[0022] The liposomal quercetin accounts for 20%-40% of the total weight of the active pharmaceutical ingredients, the genistein accounts for 15%-30% of the total weight of the active pharmaceutical ingredients, and the sodium hyaluronate accounts for 5%-10% of the total weight of the active pharmaceutical ingredients.

[0023] The polyunsaturated phospholipid choline accounts for 30%-45% of the total weight of the functional carrier material, the chitosan accounts for 20%-35% of the total weight of the functional carrier material, the poly(N-isopropylacrylamide) accounts for 25%-35% of the total weight of the functional carrier material, and the phosphatidylcholine accounts for 10%-20% of the total weight of the functional carrier material.

[0024] The iron oxide nanoparticles account for 30%-50% of the total weight of the auxiliary reinforcement material, and the carbon dot nanoparticles account for 50%-70% of the total weight of the auxiliary reinforcement material.

[0025] Glycerin accounts for 40%-60% of the total weight of the sustained-release regulator, and vitamin E acetate accounts for 40%-60% of the total weight of the sustained-release regulator.

[0026] A production process for treating body nodules, which is produced based on the above-mentioned formula for treating body nodules, comprises the following steps: S1, extracting and purifying active pharmaceutical ingredients, preparing liposomal quercetin, genistein and sodium hyaluronate; S2. preparing functional carrier materials, including preparing polyunsaturated phosphatidylcholine and phosphatidylcholine nanoparticles by emulsification-solvent evaporation method, and chitosan modification; S3, loading active pharmaceutical ingredients into functional carriers through self-assembly; S4. The functional carrier material is mixed with the active drug, and the mixture is freeze-dried or spray-dried to prepare powder or microparticles.

[0027] The specific steps of extracting and purifying the active pharmaceutical ingredient in step S1 are as follows: S1.1. Preparation of liposome quercetin: Quercetin was loaded by supercritical CO2 method, and the extraction conditions included: pressure 25-30MPa, temperature 40-55°C, and extraction time 3-4h; S1.2. Genistein is extracted by ultrasound-assisted extraction. The extraction conditions include: ultrasonic power 250-300W, extraction temperature 50-60℃, extraction time 1.5-2h. The purity of the purified genistein is ≥95%.

[0028] The specific preparation conditions of step S2 include: Oil-water ratio: 1:2-1:3; Ultrasonic power: 250-300W; Ultrasonication time: 3-5min; Solvent evaporation conditions: stirring speed 500-800 rpm, time 2-3 h; Chitosan modification was performed by electrostatic adsorption method, and the modification conditions included: chitosan concentration 15%-25%, stirring speed 300-600 rpm, and stirring time 30-60 min.

[0029] The self-assembly conditions in step S3 include: Active drug concentration: 15%-25%; Self-assembly temperature: 25-30℃; Self-assembly pH: 6.5-7.0; Self-assembly stirring speed: 300-600rpm; Self-assembly time: 30-60min.

[0030] The drying conditions for preparing the powder or microparticles in step S4 include: Freeze drying conditions: freezing temperature -40 to -60°C, drying time 12-24h; Spray drying conditions: feed temperature 100-120°C, drying time 30-60min.

[0031] Example 1: Preparation of a composite drug for treating body nodules Formula composition (weight percentage): Active pharmaceutical ingredients 20%: liposomal quercetin 10% (50% of active pharmaceutical ingredients), genistein 7% (35% of active pharmaceutical ingredients), sodium hyaluronate 3% (15% of active pharmaceutical ingredients); Functional carrier materials 70%: polyunsaturated phospholipid choline (PPC) 31.5% (accounting for 45% of the functional carrier materials), chitosan 21% (accounting for 30% of the functional carrier materials), poly (N-isopropylacrylamide) 14% (accounting for 20% of the functional carrier materials), phosphatidylcholine 3.5% (accounting for 5% of the functional carrier materials); Auxiliary reinforcement material 0.5%: iron oxide nanoparticles 0.2% (accounting for 40% of the auxiliary reinforcement material), carbon dot nanoparticles 0.3% (accounting for 60% of the auxiliary reinforcement material); Sustained-release modifier 9.5%: glycerol 5% (accounting for 52.6% of the sustained-release modifier); Vitamin E acetate 4.5% (47.4% of the sustained-release modifier) Process steps: Extraction and preparation of active drugs: Liposomal quercetin: prepared by supercritical CO2 method, pressure 28MPa, temperature 50℃, time 3.5h, purity ≥98% after purification.

[0032] Genistein: Ultrasonic-assisted extraction was used with a power of 280 W, a temperature of 55 ° C, and a time of 2 h. The purity after purification was ≥ 95%.

[0033] Sodium hyaluronate: Using water extraction method, the purity after purification is ≥95%.

[0034] Preparation of functional carrier materials: PPC and phosphatidylcholine were mixed and dissolved, the emulsification conditions were an oil-water ratio of 1:2, ultrasonic power of 280 W, time of 4 min, stirring speed of 600 rpm, and solvent evaporation for 2 h to form nanoparticles (particle size of about 120 nm).

[0035] The chitosan modification concentration was 20%, the stirring speed was 500 rpm, and the time was 45 min.

[0036] Drug loading: Active drug concentration was 20%, mixed with functional carrier at 27 °C, self-assembled for 45 min, and stirred at 500 rpm.

[0037] Drying and finished product preparation: Spray drying conditions: feed temperature 110°C, drying time 40 min, obtaining powder or microparticles with a particle size of about 200-300 nm.

[0038] Example 2: Preparation of photothermal assisted therapy drugs Formula composition (weight percentage): Active pharmaceutical ingredients 15%: liposomal quercetin 7% (46.7% of active pharmaceutical ingredients), genistein 6% (40% of active pharmaceutical ingredients), sodium hyaluronate 2% (13.3% of active pharmaceutical ingredients); Functional carrier material 75%: PPC 33.75% (accounting for 45% of the functional carrier material), chitosan 22.5% (accounting for 30% of the functional carrier material), poly (N-isopropylacrylamide) 15% (accounting for 20% of the functional carrier material), phosphatidylcholine 3.75% (accounting for 5% of the functional carrier material); Auxiliary reinforcement material 1%; Iron oxide nanoparticles 0.4% (accounting for 40% of the auxiliary reinforcement material); Carbon dot nanoparticles 0.6% (accounting for 60% of the auxiliary reinforcement material); Sustained-release regulator 9%; glycerin 4% (accounting for 44.4% of the sustained-release regulator), vitamin E acetate 5% (accounting for 55.6% of the sustained-release regulator).

[0039] Process steps: Preparation of functional carrier materials: PPC emulsification conditions: oil-water ratio 1:3, ultrasonic power 300 W, time 3.5 min, stirring speed 700 rpm, solvent evaporation time 3 h, final particle size of 100 nm.

[0040] The concentration of iron oxide particles was 0.4%, the concentration of carbon dots was 0.6%, and the modification conditions were temperature 28°C and time 60 min.

[0041] Drug loading: active drug concentration 15%, stirring speed 600 rpm after mixing, self-assembly temperature 30 °C, time 50 min.

[0042] Drying and finished product preparation: Freeze-drying conditions: freezing temperature -45°C, drying time 20h, to obtain powder or microparticles.

[0043] Example 3: Preparation of long-acting sustained-release therapeutic drugs Formula composition (weight percentage): Active pharmaceutical ingredients 18%: liposomal quercetin 9% (50% of active pharmaceutical ingredients), genistein 7% (38.9% of active pharmaceutical ingredients), sodium hyaluronate 2% (11.1% of active pharmaceutical ingredients); Functional carrier materials 67%: PPC 30.15% (accounting for 45% of functional carrier materials), chitosan 20.1% (accounting for 30% of functional carrier materials), poly (N-isopropylacrylamide) 13.4% (accounting for 20% of functional carrier materials), phosphatidylcholine 3.35% (accounting for 5% of functional carrier materials); Auxiliary reinforcement material 0.5%: iron oxide nanoparticles 0.2% (accounting for 40% of the auxiliary reinforcement material), carbon dot nanoparticles 0.3% (accounting for 60% of the auxiliary reinforcement material); Sustained-release regulator 14.5%: glycerol 7% (accounting for 48.3% of the sustained-release regulator), vitamin E acetate 7.5% (accounting for 51.7% of the sustained-release regulator).

[0044] Process steps: Drug loading: The active drug is combined with the PPC carrier, and the drug concentration is 18%. After the sustained-release agent is added, the stirring speed is 450 rpm, the temperature is 27°C, and the time is 40 minutes.

[0045] Drying and finished product preparation: Spray drying conditions: feed temperature 120°C, drying time 30 min, to obtain powder or microparticles.

[0046] Comparative Example 1: Imbalance in the ratio of active pharmaceutical ingredients (corresponding to Example 1) Recipe Adjustment: Active pharmaceutical ingredients 25%: liposomal quercetin 10% (40% of active pharmaceutical ingredients), genistein 8% (32% of active pharmaceutical ingredients), sodium hyaluronate 4% (16% of active pharmaceutical ingredients); Curcumin and Tanshinone IIA were removed.

[0047] The proportions of the other components are consistent with those in Example 1.

[0048] Process steps: Extraction and purification of active drugs: The extraction and purification process of liposomal quercetin and genistein remained consistent with Example 1.

[0049] The extraction time of sodium hyaluronate is slightly shorter, but due to the imbalance of the active drug ratio, the dissolution uniformity of the extract is poor.

[0050] Functional carrier preparation: The emulsification conditions of PPC and phosphatidylcholine remained the same as in Example 1.

[0051] The stirring speed was 500 rpm, the self-assembly time was 40 min, and the temperature was 28 °C.

[0052] Drying step: The freeze-drying conditions were kept consistent with those in Example 1: temperature -50°C, time 18 h.

[0053] Comparative Example 2: Lack of iron oxide and carbon dot reinforcement material (corresponding to Example 2) Recipe Adjustment: Auxiliary reinforcement materials: Completely remove iron oxides and carbon dot particles.

[0054] The proportions of the other components remain the same as in Example 2.

[0055] Process steps: Functional carrier preparation: The PPC emulsification conditions were consistent with those in Example 2, with an oil-water ratio of 1:3, an ultrasonic power of 300 W, and a time of 3.5 min.

[0056] Due to the omission of modification of iron oxide and carbon dot particles, the magnetic targeting property of the nanoparticles was lost and the final particle size was 110 nm.

[0057] Drug loading and drying: The drug loading concentration was maintained at 15%, the stirring speed was 600 rpm, the self-assembly temperature was 30 °C, and the time was 50 min.

[0058] Freeze drying conditions: -45°C, time 20h.

[0059] Comparative Example 3: Functional carrier loses temperature responsiveness (corresponding to Example 2) Recipe Adjustment: Removal of PNIPAM (poly(N-isopropylacrylamide)) from the functional carrier.

[0060] Functional carrier materials are adjusted to: PPC: 50% (70% of the total weight of functional carrier materials) Chitosan: 15% (accounting for 21.4% of the total weight of functional carrier materials) Phosphatidylcholine: 5% (7.1% of the total weight of the functional carrier material) Process steps: Functional carrier preparation: Emulsification was carried out according to the method of Example 2, with an oil-water ratio of 1:3, an ultrasonic power of 300 W, and a time of 3.5 min.

[0061] Due to the lack of PNIPAM, the particle size distribution of the particles is uneven, and the final average particle size is slightly larger than that of Example 2.

[0062] Drug loading and drying: The drug loading concentration was 15%, the stirring speed was 600 rpm, the self-assembly temperature was 30 °C, and the time was 45 min.

[0063] Freeze drying conditions: -45°C, time 20h.

[0064] Comparative Example 4: Reducing the proportion of sustained-release regulator (corresponding to Example 3) Recipe Adjustment: Sustained-release modifier: adjusted to 4%.

[0065] Glycerin: 2% (50% of the total weight of the sustained-release modifier) Vitamin E acetate: 2% (50% of the total weight of the sustained-release modifier) The proportions of the other components remain the same as in Example 3.

[0066] Process steps: Preparation of functional carrier materials: The amount of sustained-release regulator added was reduced by 50%, the mixing temperature was 27°C, and the mixing time was 30 min.

[0067] Drug loading and drying: drug loading concentration 18%, stirring speed 450 rpm, self-assembly time 40 min.

[0068] Freeze drying conditions: -50°C, time 24h.

[0069] Comparative Example 5: Adjusting the ratio of chitosan to phosphatidylcholine (corresponding to Example 1) Recipe Adjustment: The proportion of chitosan was increased from 30% to 50%.

[0070] The proportion of phosphatidylcholine decreased from 10% to 2%.

[0071] The proportions of the other components remain the same as in Example 1.

[0072] Process steps: Functional carrier preparation: The concentration of chitosan solution was increased to 25%, the stirring speed was 500 rpm, and the stirring time was extended to 60 min.

[0073] After the phosphatidylcholine was reduced, the emulsification time was shortened to 3 min, the stirring speed was maintained at 600 rpm, and the evaporation time remained unchanged.

[0074] Drug loading and drying: When the drug loading concentration was kept at 20%, the drug encapsulation efficiency decreased.

[0075] The freeze-drying conditions were the same as those in Example 1: -50°C, time 18 h.

[0076] Comparative Example 6: Lack of freeze drying step (corresponding to Example 3) Recipe Adjustment: All component proportions of Example 3 were kept unchanged.

[0077] Process steps: Functional carrier and drug loading: According to the method of Example 3, the drug concentration is 18%, the stirring speed is 450 rpm, and the self-assembly time is 40 min.

[0078] The freeze-drying step is omitted: the mixed drug is directly filtered to form a suspension.

[0079] Experiment 1: Drug release performance test Experimental purpose: By simulating the nodular lesion microenvironment (pH 6.5, 37°C), the sustained-release performance and cumulative release characteristics of the composite drugs of different embodiments and comparative examples were evaluated, and the effect of optimizing the ratio of sustained-release regulators and functional carriers was verified.

[0080] Experimental Materials: The composite medicines of Example 1, Example 3 and Comparative Example 1, Comparative Example 4.

[0081] Phosphate buffered saline (PBS), pH 6.5.

[0082] High performance liquid chromatography (HPLC).

[0083] Experimental steps: Sample preparation: Weigh 0.5 g of the compound drug and dissolve it in 50 mL of PBS buffer at pH 6.5.

[0084] Three parallel samples were set up in each group to ensure experimental repeatability.

[0085] Experimental conditions: The samples were placed in a constant temperature oscillator at 37°C and an oscillation speed of 100 rpm to simulate the nodule tissue microenvironment.

[0086] Sampling and testing: 2 mL of solution was taken out at 0 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h, respectively, and an equal amount of solution was supplemented with fresh PBS to ensure constant experimental conditions.

[0087] The concentrations of liposomal quercetin and genistein in the samples were detected by HPLC, and the cumulative release amounts were calculated.

[0088] Data collation and analysis: The cumulative release data were organized into tables to analyze the sustained-release performance and release differences of different samples.

[0089] Data Records: Table 1: Cumulative drug release (%) Experimental summary: Example 1 and Example 3 exhibit superior sustained-release performance. Within 48 hours, the cumulative release of Example 1 was 89.1%, while Comparative Example 1 quickly reached 96.8%, and the later drug effect lacked persistence. Example 3 released evenly in the first 24 hours, with a cumulative release of 68.7%, which was significantly better than 78.9% of Comparative Example 4. The data show that the optimized design of the sustained-release regulator and carrier in the examples significantly improves the release stability and later drug effect persistence of the drug.

[0090] Experiment 2: Drug targeted delivery performance test Experimental purpose: To evaluate the targeted delivery performance of drugs in a simulated nodular lesion environment and verify the role of magnetic and temperature response mechanisms in drug enrichment.

[0091] Experimental Materials: The composite medicines of Example 2, Example 3 and Comparative Example 2, Comparative Example 3.

[0092] Simulated lesion fluid (pH 6.5 PBS, 37°C).

[0093] Laser confocal microscopy.

[0094] Experimental steps: Sample preparation: 0.5 g of the composite drug was taken from each of the examples and comparative examples, and dissolved in 50 mL of lesion fluid to prepare a uniform dispersion.

[0095] Three parallel samples were set up in each group.

[0096] Experimental setup: The samples were divided into two groups: one group was placed under a 0.1T magnetic field, and the other group was placed without a magnetic field as a control.

[0097] Two temperatures were set at the same time: 37°C (lesion temperature) and 25°C (normal temperature control).

[0098] Sampling and testing: 2 mL of sample was taken every 2 hours to detect the drug concentration, and the enrichment of the drug in the lesion area was recorded using fluorescent labeling technology.

[0099] The sampling times are 0h, 2h, 4h, 8h, and 12h.

[0100] Data Records: Table 2: Drug accumulation in the lesion area (relative optical density unit) Experimental summary: Example 2 and Example 3 showed significant advantages in targeted delivery under the combined effects of magnetic field and temperature response. Within 12 hours, the enrichment of Example 2 reached 72.8, which was 29.2% higher than that of Comparative Example 2. Comparative Example 2 lacked magnetic materials and the drug was unevenly distributed. The synergistic effect of the temperature-responsive material PNIPAM and the magnetic iron oxide particles was the key to drug enrichment.

[0101] Experiment 3: Photothermal response performance test Experimental purpose: To verify the photothermal response performance of the composite drug and evaluate the enhancing effect of iron oxide and carbon dot particles on the photothermal conversion efficiency and drug release characteristics.

[0102] Experimental materials: Example 2, Example 3 and Comparative Example 2.

[0103] Experimental steps: Photothermal response test: The sample was placed in a transparent culture dish and irradiated with 808 nm laser at a power of 1.0 W / cm 2 , lasting 10 minutes.

[0104] The solution temperature was recorded every 1 min using an infrared thermal imager.

[0105] Drug Release Testing: After illumination, 2 mL of the sample was taken and the concentrations of liposomal quercetin and genistein were detected by HPLC to calculate the amount of drug released induced by illumination.

[0106] Data Records: Table 3: Solution temperature change in photothermal response test (°C) Experimental summary: The example groups showed remarkable photothermal response performance. Example 2 heated up to 51.9°C within 5 minutes, which was higher than 40.3°C of Comparative Example 2. This efficient photothermal conversion capability is mainly attributed to the synergistic effect of iron oxide and carbon dot particles, which can achieve more effective photothermal therapy.

[0107] Experiment 4: Drug effect persistence test Experimental purpose: To evaluate the drug efficacy persistence of the compound drug in a simulated in vivo environment, detect the drug degradation rate and long-term action time, and verify the effect of sustained-release regulators and functional carrier design on improving the drug action time.

[0108] Experimental Materials: The composite medicines of Example 1, Example 3 and Comparative Example 1, Comparative Example 4.

[0109] pH 7.4 PBS buffer.

[0110] High performance liquid chromatography (HPLC).

[0111] Experimental steps: Sample preparation: Weigh 0.5 g of the compound drug and dissolve it in 50 mL of pH 7.4 PBS buffer to simulate the in vivo physiological environment.

[0112] Three parallel samples were set up in each group.

[0113] Experimental conditions: The samples were placed in a constant temperature oscillator at 37°C and an oscillation speed of 100 rpm.

[0114] Sampling and testing: Every 24 h, 2 mL of sample was taken and an equal amount of solution was supplemented with fresh PBS to maintain constant experimental conditions.

[0115] The residual concentrations of liposomal quercetin and genistein were detected by HPLC, and the residual percentages were recorded.

[0116] Data collation and analysis: The drug residue percentage data were organized into tables to analyze drug degradation rate and duration of action.

[0117] Data Records: Table 4: Changes in drug residue percentage (%) over time Experimental summary: Examples 1 and 3 exhibited excellent drug efficacy persistence. Within 96 hours, the residual drug in Example 1 was 42.3%, while that in Comparative Example 1 was only 10.9%, indicating that the synergistic effect of glycerol and vitamin E acetate effectively delayed the drug degradation process. The residual drug in Example 3 was 47.9%, significantly better than 29.5% in Comparative Example 4. The data show that the optimized ratio of sustained-release regulator and carrier can prolong the drug's duration of action and reduce the frequency of medication.

[0118] Experiment 5: Particle dispersion and stability test Experimental purpose: To evaluate the dispersibility and stability of functional carrier materials in different solution environments, to determine the particle size and sedimentation characteristics by dynamic light scattering (DLS), and to verify the effect of optimizing the proportion of carrier materials.

[0119] Experimental Materials: The composite medicines of Example 1, Example 2 and Comparative Example 3 and Comparative Example 5.

[0120] Deionized water, pH 7.4 PBS buffer.

[0121] Dynamic Light Scattering (DLS).

[0122] Experimental steps: Sample preparation: Take 0.5 g of the compound drug from each group of samples, add it to 10 mL of deionized water or PBS buffer, and ultrasonically disperse it for 30 seconds to prepare a uniform drug solution.

[0123] Particle size distribution determination: DLS was used to measure the initial particle size and polydispersity index (PDI).

[0124] After the sample was left to stand for 24 h, the particle size and PDI were re-measured.

[0125] Stability observation: Record the sedimentation of the sample after standing for 24 hours, including whether particle aggregation and sedimentation occur.

[0126] Data Records: Table 5: Nanoparticle size and stability test data Experimental summary: The dispersibility and stability of the nanoparticles in the solution of the embodiment group are better than those of the comparative example group. The particle size of Examples 1 and 2 changes little, and there is no sedimentation after 24 hours, while the particles of Comparative Examples 3 and 5 aggregate and settle due to unreasonable carrier ratio design. The optimized carrier ratio significantly improves the particle stability, providing a guarantee for drug storage and transportation.

[0127] Experiment 6: Tissue absorption and adhesion test Experimental purpose: To evaluate the absorption and adhesion performance of the composite drug in a simulated nodule tissue environment and to verify the synergistic effect of sodium hyaluronate and functional carrier materials on the improvement of drug absorption and retention.

[0128] Experimental Materials: The composite medicines of Example 1, Example 2 and Comparative Example 1 and Comparative Example 5.

[0129] pH 7.4 PBS buffer.

[0130] Gelatin solution (5%, w / v).

[0131] Experimental steps: Sample preparation: 0.5 g of the compound drug was taken from each group of samples, dissolved in 10 mL of PBS buffer, and ultrasonically dispersed for 30 seconds to prepare a uniform drug solution.

[0132] Preparation of simulated nodule tissue matrix: Heat 5% gelatin solution to 40°C and cool to room temperature to solidify.

[0133] Experimental setup: Add 2 mL of drug solution to the substrate surface and let it stand for 5 minutes.

[0134] The matrix was placed in a shaker (50 rpm) at 37°C to simulate in vivo conditions.

[0135] Sampling and testing: At 6 h, 12 h, 24 h, and 36 h, the residual drug solution on the surface of the matrix was cleaned, the drug concentration in the matrix was detected by HPLC, and the drug adsorption rate was calculated.

[0136] Data Records: Table 6: Drug adsorption rate of simulated nodule matrix (%) Experimental summary: The introduction of sodium hyaluronate significantly improved the absorption performance of the drug. The adsorption rates of Example 1 and Example 2 reached 76.2% and 80.1% respectively within 36 hours, which were much higher than those of Comparative Example 1 and Comparative Example 5. This shows that the optimized carrier and active ingredient design can effectively enhance the retention performance of the drug in the target area, thereby improving the therapeutic effect.

[0137] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A formula for treating body nodules, characterized in that: By weight percentage, it includes the following components: Active pharmaceutical ingredients: 15%-25%; Functional carrier material: 65%-80%; Auxiliary reinforcement materials: 0.2%-1%; Sustained-release modifier: 5%-10%; in: The active pharmaceutical ingredients include liposomal quercetin, genistein, and sodium hyaluronate; The functional carrier material includes polyunsaturated phosphatidylcholine, chitosan, poly(N-isopropylacrylamide) and phosphatidylcholine; The auxiliary reinforcement material includes iron oxide nanoparticles and carbon dot nanoparticles; The sustained-release regulator includes glycerin and vitamin E acetate.

2. A formulation for treating body nodules according to claim 1, characterized in that: The liposomal quercetin accounts for 20%-40% of the total weight of the active pharmaceutical ingredients, genistein accounts for 15%-30% of the total weight of the active pharmaceutical ingredients, and sodium hyaluronate accounts for 5%-10% of the total weight of the active pharmaceutical ingredients.

3. A formulation for treating body nodules according to claim 1, characterized in that: The polyunsaturated phospholipid choline accounts for 30%-45% of the total weight of the functional carrier material, chitosan accounts for 20%-35% of the total weight of the functional carrier material, poly (N-isopropylacrylamide) accounts for 25%-35% of the total weight of the functional carrier material, and phosphatidylcholine accounts for 10%-20% of the total weight of the functional carrier material.

4. A formulation for treating body nodules according to claim 1, characterized in that: The iron oxide nanoparticles account for 30%-50% of the total weight of the auxiliary reinforcement material, and the carbon dot nanoparticles account for 50%-70% of the total weight of the auxiliary reinforcement material.

5. A formulation for treating body nodules according to claim 1, characterized in that: The glycerol accounts for 40%-60% of the total weight of the sustained-release regulator, and the vitamin E acetate accounts for 40%-60% of the total weight of the sustained-release regulator.

6. A production process for treating body nodules, characterized in that: The production of a formulation for treating body nodules according to any one of claims 1 to 5 comprises the following steps: S1, extracting and purifying active pharmaceutical ingredients, preparing liposomal quercetin, genistein and sodium hyaluronate; S2. preparing functional carrier materials, including preparing polyunsaturated phosphatidylcholine and phosphatidylcholine nanoparticles by emulsification-solvent evaporation method, and chitosan modification; S3, loading active pharmaceutical ingredients into functional carriers through self-assembly; S4. The functional carrier material is mixed with the active drug, and the mixture is freeze-dried or spray-dried to prepare powder or microparticles.

7. A production process for treating body nodules according to claim 6, characterized in that: The specific steps of extracting and purifying the active pharmaceutical ingredient in step S1 are as follows: S1.

1. Preparation of liposome quercetin: Quercetin was loaded by supercritical CO2 method, and the extraction conditions included: pressure 25-30MPa, temperature 40-55°C, and extraction time 3-4h; S1.

2. Genistein is extracted by ultrasound-assisted extraction. The extraction conditions include: ultrasonic power 250-300W, extraction temperature 50-60℃, extraction time 1.5-2h. The purity of the purified genistein is ≥95%.

8. The production process for treating body nodules according to claim 6, characterized in that: The specific preparation conditions of step S2 include: Oil-water ratio: 1:2-1:3; Ultrasonic power: 250-300W; Ultrasonication time: 3-5min; Solvent evaporation conditions: stirring speed 500-800 rpm, time 2-3 h; The chitosan modification is performed by an electrostatic adsorption method, and the modification conditions include: chitosan concentration of 15%-25%, stirring speed of 300-600 rpm, and stirring time of 30-60 min.

9. The production process for treating body nodules according to claim 6, characterized in that: The self-assembly conditions in the S3 step include: Active drug concentration: 15%-25%; Self-assembly temperature: 25-30℃; Self-assembly pH: 6.5-7.0; Self-assembly stirring speed: 300-600rpm; Self-assembly time: 30-60min.

10. The production process for treating body nodules according to claim 6, characterized in that: The drying conditions for preparing the powder or particles in step S4 include: Freeze drying conditions: freezing temperature -40 to -60°C, drying time 12-24h; Spray drying conditions: feed temperature 100-120°C, drying time 30-60min.

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