Lower limb wound treatment ointment based on traditional Chinese medicine and preparation method thereof

Abstract

The invention relates to the technical field of physical education, and provides a lower limb wound treatment ointment based on traditional Chinese medicine. The coating is prepared from the following components in percentage by weight: 5 to 15 percent of medicinal powder mixture, 15 to 25 percent of polylactic acid-glycolic acid copolymer, 1 to 3 percent of poly (N-isopropylacrylamide), 1 to 3 percent of polyacrylate, 30 to 40 percent of vegetable oil, 5 to 10 percent of glycerol and 10 to 20 percent of deionized water. The invention further provides a preparation method of the lower limb wound treatment ointment based on the traditional Chinese medicine. The preparation method comprises the following steps: S1, crushing cortex phellodendri, radix sophorae flavescentis, radix arnebiae seu lithospermi, radix angelicae sinensis and fructus lycii into 80-120-mesh powder, and mixing to obtain a medicinal powder mixture; by adopting a PLGA microcapsule wrapping technology, the medicine is effectively encapsulated in the microcapsule, so that the stability of the medicine is ensured, and the release time is prolonged. Compared with the mode of directly mixing the medicine and the matrix in the prior art, the problem of quick release of the medicine is avoided through the slow release characteristic of the microcapsule, so that the medicine can continuously play a role, and particularly, the curative effect can be better ensured in long-term treatment of the wound surface.

Description

Technical Field

[0001] The present invention relates to the technical field of physical education teaching, and specifically to a lower limb wound treatment ointment based on traditional Chinese medicine and its preparation method. Background Art

[0002] As a commonly used local treatment method, wound treatment ointments play an important role in the treatment of various wounds such as skin wounds, burns, and ulcers. Existing wound treatment ointments mainly achieve wound healing through the external penetration of drugs and local efficacy. However, despite the availability of a variety of wound treatment ointment products on the market, there are still some technical deficiencies and drawbacks.

[0003] Most of the drug release methods of traditional wound treatment ointments are one-time rapid release, resulting in the rapid action of the drug in a short time, followed by a decline in the effect. This non-sustained release of the drug makes it impossible to maintain the treatment process at an effective drug concentration level, and changes in the local wound environment, such as fluctuations in temperature and pH value, will affect the drug effect. Existing ointment formulations cannot be dynamically adjusted according to these changes, resulting in inefficient and unstable drug use effects.

[0004] Most of the drug components in wound treatment ointments are directly mixed in the matrix, lacking effective control over drug release. This method leads to uneven drug release, which may result in over-release or under-release, causing unstable drug efficacy.

[0005] The matrix of existing ointments usually only relies on a single oil-based component or water-based component to adjust the viscosity and lubricity of the ointment. Although this method can ensure the wetness of the wound to a certain extent, the effect is limited. After long-term use, the wound often shows phenomena such as cracking and peeling, resulting in a reduction in the treatment effect. Summary of the Invention

[0006] Aiming at the deficiencies of the existing technology, the present invention provides a lower limb wound treatment ointment based on traditional Chinese medicine and its preparation method, which solves the problems of too fast, uneven drug release rate, lack of dynamic regulation, and insufficient maintenance of wound wetness in the ointment.

[0007] To achieve the above objectives, the present invention is realized through the following technical solutions: A lower limb wound treatment ointment based on traditional Chinese medicine, by weight percentage, includes the following components;

[0008] Powder mixture 5 - 15%, poly(lactic-co-glycolic acid) 15 - 25%, poly(N-isopropylacrylamide) 1 - 3%, polyacrylate 1 - 3%, vegetable oil 30 - 40%, glycerol 5 - 10%, and deionized water 10 - 20%.

[0009] Preferably, the medicinal powder mixture includes 30-40% of Phellodendron amurense, 20-30% of Sophora flavescens, 15-25% of Lithospermum erythrorhizon, 10-15% of Angelica sinensis, and 5-10% of Lycium barbarum, and is obtained by crushing and mixing Phellodendron amurense, Sophora flavescens, Lithospermum erythrorhizon, Angelica sinensis, and Lycium barbarum.

[0010] Preferably, the poly(lactic-co-glycolic acid) is prepared by condensation polymerization of lactic acid and glycolic acid.

[0011] A preparation method of a lower limb wound treatment ointment based on traditional Chinese medicine. The method comprises the following steps;

[0012] S1. Crush Phellodendron amurense, Sophora flavescens, Lithospermum erythrorhizon, Angelica sinensis, and Lycium barbarum into powders with a mesh size of 80-120, and mix them to obtain a medicinal powder mixture;

[0013] S2. Dissolve the medicinal powder mixture and poly(lactic-co-glycolic acid) in an organic solvent, and use the solvent evaporation method to prepare microcapsules to form a drug carrier;

[0014] S3. Mix the microcapsules with poly(N-isopropylacrylamide) and polyacrylate, and perform coating to obtain environmentally responsive microcapsules;

[0015] S4. Mix vegetable oil, glycerol, and deionized water, and stir at 50-70 °C for 30-60 min to form a uniform matrix;

[0016] S5. Add the environmentally responsive microcapsules to the matrix and stir for 20-50 min to obtain a uniformly dispersed ointment;

[0017] S6. Perform homogenization treatment and fill it into a container to obtain the finished ointment.

[0018] Preferably, in step S2, the particle size of the microcapsules is controlled within 200-500 nm, and the drug entrapment efficiency is 70-90%.

[0019] Preferably, in step S2, the temperature of the solvent evaporation method is controlled within 40-60 °C, the solvent evaporation process time is 1-3 h, and the organic solvent is dichloromethane.

[0020] Preferably, in step S3, the coating thickness of poly(N-isopropylacrylamide) and polyacrylate is 50-200 nm.

[0021] Preferably, in step S4, the mass ratio of vegetable oil to glycerol is 3:1 to 5:1, and the stirring rate is 300-800 rpm.

[0022] Preferably, in step S5, the stirring temperature is 25-40 °C, and the stirring time is 20-60 min to ensure uniform mixing of the drug and the matrix.

[0023] Preferably, in step S6, the homogenization treatment is carried out using a homogenizer at 8000 - 15000 rpm, and the homogenization time is 3 - 10 min.

[0024] The present invention provides a traditional Chinese medicine - based lower limb wound treatment ointment and its preparation method. It has the following beneficial effects:

[0025] 1. By adopting the PLGA microcapsule encapsulation technology, the present invention effectively encapsulates the drug in the microcapsules, ensuring the stability of the drug and prolonging the release time. Compared with the prior art of directly mixing the drug with the matrix, through the slow - release characteristics of the microcapsules, the problem of rapid drug release is avoided, enabling the drug to continuously play its role. Especially in the long - term treatment of wounds, the curative effect can be more ensured.

[0026] 2. By introducing temperature - responsive poly(N - isopropylacrylamide), the present invention adjusts the drug release rate according to the change of wound temperature. When the wound is at a higher temperature, the swelling effect of PNIPAM can accelerate drug release. Compared with the static release mode of existing ointments, it can adaptively adjust drug release according to different temperature states of the wound, effectively controlling the influence brought by the change of wound temperature.

[0027] 3. By combining polyacrylate as a pH - responsive material, the present invention can adjust the drug release rate when the pH value of the wound changes. During wound infection or inflammation, the pH value changes, and the addition of polyacrylate can quickly respond to this change, optimizing the timing and amount of drug release, thereby enhancing the curative effect. Compared with the ointments in the prior art that do not consider the change of wound pH value, the present invention can more accurately adapt to the local environment of the wound and ensure the treatment effect.

[0028] 4. By adopting a composite formula of vegetable oil and glycerol, the present invention not only enhances the moisturizing property of the ointment but also provides a continuous lubricating effect, reducing wound cracking. In the prior art, most traditional ointments rely on a single oil - based component and lack the long - term wet - keeping effect. Relatively speaking, the present invention can provide a better wet environment during wound repair, contributing to accelerating wound healing and reducing scar formation. Brief Description of the Drawings

[0029] Figure 1 It is a flowchart of the method of the present invention. Detailed Embodiments

[0030] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0031] Example

[0032] Please refer to the attached Figure 1 , the embodiments of the present invention provide a traditional Chinese medicine-based lower limb wound treatment ointment, which includes the following components by weight percentage;

[0033] Powder mixture 5 - 15%, poly(lactic-co-glycolic acid) 15 - 25%, poly(N-isopropylacrylamide) 1 - 3%, polyacrylate 1 - 3%, vegetable oil 30 - 40%, glycerol 5 - 10%, and deionized water 10 - 20%.

[0034] The powder mixture includes 30 - 40% Phellodendron amurense, 20 - 30% Sophora flavescens, 15 - 25% Lithospermum erythrorhizon, 10 - 15% Angelica sinensis, and 5 - 10% Lycium barbarum, and is obtained by crushing and mixing Phellodendron amurense, Sophora flavescens, Lithospermum erythrorhizon, Angelica sinensis, and Lycium barbarum.

[0035] The poly(lactic-co-glycolic acid) is prepared by condensation polymerization of lactic acid and glycolic acid.

[0036] A preparation method of a traditional Chinese medicine-based lower limb wound treatment ointment includes the following steps;

[0037] S1. Crush Phellodendron amurense, Sophora flavescens, Lithospermum erythrorhizon, Angelica sinensis, and Lycium barbarum into powders with a mesh size of 80 - 120, and mix them to obtain a powder mixture;

[0038] S2. Dissolve the powder mixture and poly(lactic-co-glycolic acid) in an organic solvent, and use the solvent evaporation method to prepare microcapsules to form a drug carrier;

[0039] S3. Mix the microcapsules with poly(N-isopropylacrylamide) and polyacrylate, and perform coating to obtain environmentally responsive microcapsules;

[0040] S4. Mix the vegetable oil, glycerol, and deionized water, and stir at 50 - 70 °C for 30 - 60 min to form a uniform matrix;

[0041] S5. Add the environmentally responsive microcapsules to the matrix, and stir for 20 - 50 min to obtain a uniformly dispersed ointment;

[0042] S6. Perform homogenization treatment and fill it into a container to obtain the finished ointment.

[0043] Example 1;

[0044] Group allocation ratio;

[0045] Powder mixture; 10%

[0046] (Phellodendron amurense Rupr. 35%, Sophora flavescens Aiton 25%, Lithospermum erythrorhizon Sieb. et Zucc. 20%, Angelica sinensis (Oliv.) Diels 15%, and Lycium barbarum L. 5%)

[0047] Poly(lactic-co-glycolic acid) (PLGA); 20%

[0048] Poly(N-isopropylacrylamide) (PNIPAM); 2%

[0049] Polyacrylate; 2%

[0050] Vegetable oil; 32%

[0051] Glycerol; 7%

[0052] Deionized water; 17%

[0053] Powder preparation: Weigh Phellodendron amurense Rupr., Sophora flavescens Aiton, Lithospermum erythrorhizon Sieb. et Zucc., Angelica sinensis (Oliv.) Diels, and Lycium barbarum L. according to the ratio, and crush them to 80 - 120 mesh to ensure the uniformity of the medicinal material powder for subsequent mixing.

[0054] PLGA microcapsule preparation: Add the powder mixture and PLGA to the solvent (dichloromethane) according to the ratio, stir evenly, and then use the solvent evaporation method to prepare microcapsules. Set the temperature at 50°C, the evaporation time at 2 h, and control the microcapsule particle size at 300 nm.

[0055] Coating reaction: Mix the microcapsules with PNIPAM and polyacrylate for coating. Place the coated microcapsules at 45°C and control the coating thickness at 150 nm.

[0056] Matrix preparation: Mix vegetable oil and glycerol in a mass ratio of 4:1, stir at 60°C for 40 min until the oil matrix is fully dissolved. Add deionized water and continue to stir for 20 min to ensure uniformity.

[0057] Mixing and uniform dispersion: Add the coated microcapsules to the matrix, keep the temperature at 30°C, and stir for 40 min to ensure that the microcapsules are uniformly dispersed in the matrix.

[0058] Homogenization treatment: Use a homogenizer at 15000 rpm for homogenization treatment for 5 min to ensure the uniformity of the ointment.

[0059] Finished product packaging: After the ointment is completed, pack it into a sealed container and store it at room temperature.

[0060] Example 2;

[0061] Group allocation ratio;

[0062] Powder mixture; 12%

[0063] (Phellodendron amurense Rupr. 40%, Sophora flavescens Ait. 30%, Lithospermum erythrorhizon Sieb. et Zucc. 15%, Angelica sinensis (Oliv.) Diels 10%, and Lycium barbarum L. 5%)

[0064] Poly(lactic-co-glycolic acid) (PLGA); 18%

[0065] Poly(N-isopropylacrylamide) (PNIPAM); 3%

[0066] Polyacrylate; 2%

[0067] Vegetable oil; 30%

[0068] Glycerol; 8%

[0069] Deionized water; 17%

[0070] Preparation steps;

[0071] Powder mixing: Phellodendron amurense Rupr., Sophora flavescens Ait., Lithospermum erythrorhizon Sieb. et Zucc., Angelica sinensis (Oliv.) Diels, and Lycium barbarum L. are respectively pulverized to 100 mesh and mixed with a standard laboratory mixer to ensure complete uniformity of the medicinal material powders.

[0072] Microcapsule preparation: PLGA is mixed with the powder, an appropriate amount of organic solvent (dichloromethane) is added, and microencapsulation is carried out by the emulsion-solvent evaporation method. The solvent evaporation temperature is controlled at 55 °C for 3 h, and the microcapsule particle size is maintained at about 300 nm.

[0073] Coating reaction: The coating materials PNIPAM and polyacrylate are dissolved in proportion and coated on the surface of the microcapsules. The coating thickness is controlled at 100 nm, and the reaction time is 30 min to ensure uniform coverage of the outer layer material.

[0074] Matrix preparation: Vegetable oil and glycerol are mixed at a ratio of 3:1, stirred at 50 °C for 30 min, then deionized water is added, and stirring is continued for 20 min to form a uniform matrix.

[0075] Mixing of microcapsules and matrix: The coated microcapsules are added to the matrix, and stirred with a constant temperature stirrer at 30 °C for 40 min to ensure uniform dispersion of the drug carrier.

[0076] Homogenization and packaging: Homogenization is carried out with a homogenizer at 10,000 rpm for 5 min to ensure uniform quality of the ointment, and finally filled into sterile containers.

[0077] Example 3;

[0078] Component ratio;

[0079] Powder mixture; 8%

[0080] (Phellodendron amurense Rupr. 33%, Sophora flavescens Aiton 27%, Lithospermum erythrorhizon Sieb. et Zucc. 20%, Angelica sinensis (Oliv.) Diels 15%, and Lycium barbarum L. 5%)

[0081] Poly(lactic-co-glycolic acid) (PLGA); 22%

[0082] Poly(N-isopropylacrylamide) (PNIPAM); 2%

[0083] Polyacrylate; 1%

[0084] Vegetable oil; 35%

[0085] Glycerol; 5%

[0086] Deionized water; 13%

[0087] Preparation steps;

[0088] Powder mixing: The Chinese herbal medicines Phellodendron amurense Rupr., Sophora flavescens Aiton, Lithospermum erythrorhizon Sieb. et Zucc., Angelica sinensis (Oliv.) Diels, and Lycium barbarum L. are crushed according to the above proportions and mixed evenly. A ball mill is used for crushing to ensure that the powder fineness reaches 90 mesh.

[0089] Microcapsule preparation: The powder mixture and PLGA are dissolved in dichloromethane, and microcapsules are prepared by the solvent evaporation method. The solvent evaporation temperature is controlled at 60 °C for 2 h, and the microcapsule particle size is maintained at 200 nm.

[0090] Coating layer preparation: PNIPAM and polyacrylate are dissolved in proportion and mixed with the microcapsules, and coated evenly. The coating thickness is controlled at 50 nm, and the coating reaction is carried out at 45 °C for 30 min.

[0091] Matrix formulation: Vegetable oil and glycerol are mixed in a ratio of 4:1 and stirred at 40 °C for 30 min to ensure complete fusion, and then deionized water is added and stirred until uniform.

[0092] Adding microcapsules to the matrix: The coated microcapsules are added to the matrix and stirred at 30 °C for 50 min to ensure uniform dispersion of the drug.

[0093] Homogenization and shaping: A homogenizer is used, with the speed set at 12000 rpm and the homogenization time at 5 min to ensure the uniformity and stability of the ointment. Finally, it is filled into a sterile container and sealed for storage.

[0094] Example 4;

[0095] Component ratio;

[0096] Powder mixture; 10%

[0097] (Phellodendron amurense Rupr. 35%, Sophora flavescens Aiton 25%, Lithospermum erythrorhizon Sieb. et Zucc. 20%, Angelica sinensis (Oliv.) Diels 15%, and Lycium barbarum L. 5%)

[0098] Poly(lactic-co-glycolic acid) (PLGA); 18%

[0099] Poly(N-isopropylacrylamide) (PNIPAM); 2%

[0100] Polyacrylate; 2%

[0101] Vegetable oil; 30%

[0102] Glycerol; 8%

[0103] Deionized water; 15%

[0104] Preparation steps;

[0105] Preparation of medicinal powder: Crush all medicinal materials according to the ratio, and use an ultrasonic crusher for treatment to ensure that the fineness of the medicinal powder reaches 80 mesh and is evenly mixed.

[0106] Preparation of PLGA microcapsules: Dissolve the medicinal powder and PLGA in dichloromethane according to the ratio, and prepare microcapsules by the emulsion-solvent evaporation method. The evaporation temperature is 50 °C, and the evaporation time is controlled at 2 h to obtain microcapsules with a particle size of 250 - 300 nm.

[0107] Preparation of coating layer: Dissolve PNIPAM and polyacrylate according to the ratio and coat it on the surface of the microcapsules. The coating thickness is controlled at 100 nm, the temperature during the coating process is 45 °C, and the time is controlled at 30 min.

[0108] Preparation of matrix: Mix vegetable oil and glycerol in a ratio of 3:1, add deionized water and stir evenly. The stirring temperature is controlled at 60 °C for 40 min.

[0109] Mixing of microcapsules and matrix: Add the coated microcapsules to the matrix, use a constant-temperature stirrer to keep the stirring temperature at 30 °C for 40 min to ensure uniform dispersion.

[0110] Homogenization and packaging: Put the ointment into a homogenizer for treatment at a speed of 10000 rpm for 5 min, and finally fill it into a container and seal it for storage.

[0111] Comparative example 1; Traditional ointment formula, without microcapsule encapsulation

[0112] Component ratio;

[0113] Medicinal powder mixture; 12%

[0114] (Phellodendron amurense 35%, Sophora flavescens 25%, Lithospermum erythrorhizon 20%, Angelica sinensis 15% and Lycium barbarum 5%)

[0115] Vegetable oil; 32%

[0116] Glycerol; 7%

[0117] Deionized water; 17%

[0118] Preparation steps;

[0119] Medicinal powder mixing: Crush the medicinal materials to 80 mesh and mix them according to the ratio to ensure uniformity.

[0120] Matrix preparation: Mix vegetable oil and glycerol in a ratio of 3:1, add deionized water, and stir at 60 °C for 40 min to ensure the stability of the matrix.

[0121] Mixing and dispersion: Add the medicinal material powder to the matrix and stir for 30 min to uniformly disperse the drug.

[0122] Homogenization treatment: Use a homogenizer for homogenization, set the speed to 10000 rpm, and the homogenization time to 5 min to ensure the uniformity of the ointment.

[0123] Finished product packaging: Pack the finished ointment into a sterile container and store it sealed.

[0124] Comparative Example 2; Traditional microencapsulation technology, without temperature and pH responsiveness regulation

[0125] Component ratio;

[0126] Medicinal powder mixture; 12%

[0127] (Phellodendron amurense 35%, Sophora flavescens 25%, Lithospermum erythrorhizon 20%, Angelica sinensis 15%, and Lycium barbarum 5%)

[0128] Poly(lactic-co-glycolic acid) (PLGA); 20%

[0129] Vegetable oil; 32%

[0130] Glycerol; 7%

[0131] Deionized water; 17%

[0132] Preparation steps;

[0133] Medicinal powder preparation: Crush the medicinal materials to 80 mesh according to the ratio and mix them evenly.

[0134] Microcapsule preparation: Add the medicinal powder and PLGA to the solvent, and use the solvent evaporation method to prepare microcapsules. The solvent evaporation temperature is 55 °C for 2 h, and the microcapsule particle size is 300 nm.

[0135] Matrix preparation: Mix vegetable oil and glycerol in a ratio of 3:1, stir at 60 °C for 40 min, and add deionized water and stir until uniform.

[0136] Microcapsule and matrix mixing: Add the PLGA microcapsules to the matrix and stir for 40 min to ensure the uniform dispersion of the microcapsules.

[0137] Homogenization and packaging; perform homogenization treatment with a homogenization speed set at 10,000 rpm for 5 minutes, and then load it into a sterile container.

[0138] Comparative Example 3; no temperature-responsive microcapsules, only using pH-responsive materials

[0139] Component ratio;

[0140] Powder mixture; 12%

[0141] (Phellodendron amurense Rupr. 35%, Sophora flavescens Aiton 25%, Lithospermum erythrorhizon Sieb. et Zucc. 20%, Angelica sinensis (Oliv.) Diels 15%, and Lycium barbarum L. 5%)

[0142] Poly(lactic-co-glycolic acid) (PLGA); 20%

[0143] Polyacrylate; 3%

[0144] Vegetable oil; 30%

[0145] Glycerol; 7%

[0146] Deionized water; 18%

[0147] Preparation steps;

[0148] Powder mixing; Mix the powders in proportion and grind them to 80 mesh.

[0149] PLGA microcapsule preparation; Add the powder mixture and PLGA to a solvent in proportion and use the solvent evaporation method to prepare microcapsules. The evaporation temperature is 55°C for 2 hours, and the microcapsule particle size is 300 nanometers.

[0150] pH-responsive coating; Dissolve the polyacrylate and coat it on the surface of the PLGA microcapsules. The coating thickness is 100 nanometers.

[0151] Matrix preparation; Mix vegetable oil and glycerol in a ratio of 3:1, add deionized water, stir evenly, at a temperature of 60°C for 40 minutes.

[0152] Mixing and uniform dispersion; Add the coated microcapsules to the matrix and stir with a constant temperature stirrer for 40 minutes.

[0153] Homogenization treatment; Use a homogenizer for homogenization, with a homogenization speed of 12,000 rpm for 5 minutes to ensure uniformity.

[0154] Packaging; Load the ointment into a sealed container for storage.

[0155] Comparative Example 4; Microcapsules combined with a single matrix component

[0156] Component ratio;

[0157] Powder mixture; 10%

[0158] (35% Phellodendron amurense, 25% Sophora flavescens, 20% Lithospermum erythrorhizon, 15% Angelica sinensis, and 5% Lycium barbarum)

[0159] Poly(lactic-co-glycolic acid) (PLGA); 18%

[0160] Poly(N-isopropylacrylamide) (PNIPAM); 2%

[0161] Polyacrylate; 2%

[0162] Vegetable oil; 40%

[0163] Glycerol; 8%

[0164] Deionized water; 12%

[0165] Preparation steps;

[0166] Powder mixing; The medicinal materials are crushed according to the proportion to 100 mesh to ensure the uniformity of the drug components.

[0167] Microcapsule preparation; The powder and PLGA are added to the solvent according to the proportion, and microcapsules are prepared by the solvent evaporation method. The solvent evaporation temperature is 60 °C, the evaporation time is 2 h, and the microcapsule particle size is 250 nm.

[0168] Coating treatment; After dissolving PNIPAM and polyacrylate, they are coated on the surface of the microcapsules, and the coating thickness is controlled to be 100 nm.

[0169] Matrix preparation; Vegetable oil and glycerol are mixed, stirred at 60 °C for 45 min, and deionized water is added and stirred evenly to form a matrix.

[0170] Adding microcapsules to the matrix; The coated microcapsules are added to the matrix and stirred for 40 min to ensure uniform dispersion of the drug.

[0171] Homogenization treatment; Homogenization is carried out using a homogenizer at 15000 rpm for 6 min to ensure the uniformity of the ointment.

[0172] Packaging; The final product is filled into a sterile container and sealed for storage.

[0173] Experiment 1; Drug release rate comparison experiment

[0174] Experiment purpose;

[0175] This experiment aims to prove the advantages of the present invention in terms of drug release persistence and precision by comparing the drug release rates of Example 1 (PLGA microcapsules combined with responsive materials) and Comparative Example 1 (traditional ointment without microcapsules).

[0176] Experiment method;

[0177] Experimental group setting;

[0178] Experimental group 1; Example 1 (PLGA microcapsule + PNIPAM + polyacrylate)

[0179] Experimental group 2; Comparative example 1 (without microcapsule technology)

[0180] Sample preparation;

[0181] Prepare ointments according to the formulas of Example 1 and Comparative example 1 respectively. All formulas are accurately weighed according to the component ratios to ensure the same precision for each formula. Standard equipment is used for mixing and homogenizing the ointments in the experiment to maintain the consistency of the ointments.

[0182] Drug release experiment;

[0183] Simulate the wound environment; evenly apply about 1 g of ointment on the surface of artificial skin. Immerse the sample after applying the ointment in physiological saline at 37 °C to simulate the skin environment.

[0184] Sampling and analysis; every 30 min, use filter paper to absorb part of the solution for sampling until the drug is completely released. Use high performance liquid chromatography (HPLC) to measure the drug concentration.

[0185] Data recording;

[0186] Record the relationship between the cumulative percentage of drug release and time. The experiment lasts for 24 h, record the drug concentration for each sampling, and plot the release curve.

[0187] Experiment setting;

[0188] Measure drug release at intervals, compare the release time, release rate and total release amount of the two groups. The experiment is divided into two groups to compare the drug release curves of Example 1 and Comparative example 1.

[0189] Experiment data;

[0190] Time (h) Drug release amount of Example 1 (%) Drug release amount of Comparative Example 1 (%) 0.5 8.2 15.5 1.0 15.3 30.0 2.0 25.7 45.1 3.0 34.1 60.3 4.0 39.8 70.5 5.5 45.2 80.0 7.0 50.0 85.5 9.0 55.1 90.3 12.0 58.7 92.4 15.0 63.4 93.1 20.0 68.2 94.5 24.0 72.5 95.2

[0191] Table name; Comparative data table of drug release rate

[0192] Summary;

[0193] In Example 1, the introduction of PLGA microcapsules enables the drug to be released slowly and continuously. The drug release rate is significantly lower than that of Comparative example 1. The encapsulation of the drug by PLGA microcapsules plays a key role in reducing the early release of the drug. In contrast, Comparative example 1 without microcapsules has a higher release amount and a faster release rate in the first few hours, and the drug is not effectively controlled, resulting in a less durable therapeutic effect than Example 1.

[0194] PLGA microcapsules degrade slowly in the simulated wound environment through hydrolysis, thus achieving the sustained release of drugs. The addition of PNIPAM and polyacrylate further precisely regulates the drug release rate, ensuring that the drug can be released as needed under different states of the wound. The presence of temperature and pH-responsive materials means that drug release is not only controlled by time but can also be adjusted according to changes in the wound environment, which further improves the therapeutic effect of the drug.

[0195] The drug release in Example 1 was stable and continuous within 24 hours, while the drug release in Comparative Example 1 reached a relatively high level almost at the beginning. The combination of PLGA microcapsules and responsive materials can effectively solve the technical problems of too fast or uneven drug release in existing ointment preparations.

[0196] Experiment 2; Comparative experiment on wound healing effect

[0197] Purpose of the experiment;

[0198] The purpose of this experiment is to compare the effects of Example 2 (PLGA microcapsules + PNIPAM + polyacrylate + vegetable oil / glycerol matrix) and Comparative Example 2 (PLGA microcapsules + traditional matrix, lacking PNIPAM and polyacrylate) in wound healing, and to verify the advantages of the present invention in promoting wound healing.

[0199] Experimental method;

[0200] Setting of experimental groups;

[0201] Experimental group 1; Example 2 (PLGA microcapsules + PNIPAM + polyacrylate + vegetable oil / glycerol matrix)

[0202] Experimental group 2; Comparative Example 2 (PLGA microcapsules + traditional matrix, lacking PNIPAM and polyacrylate)

[0203] Experimental animals and wound models;

[0204] Standardized animals (such as mice) were selected for the experiment, and a standardized skin wound model was established. The diameter of the wound was set to 1 cm, and the depth of the wound was controlled at the epidermal layer.

[0205] Observation during postoperative recovery, keeping the animals in a temperature-controlled environment to ensure the minimum interference of other factors on the experimental results.

[0206] Ointment application;

[0207] The wounds on the backs of the animals were smeared with the ointment prepared in Example 2 or Comparative Example 2 once a day for 7 consecutive days. The application amount was 1 g to ensure complete coverage of the entire wound.

[0208] Observation indicators;

[0209] Healing time; Record the time when the wound heals completely and observe whether the wound is completely closed.

[0210] Degree of healing; Regularly record the area change of the wound by taking pictures and measuring the wound area, and quantitatively analyze the healing situation using image analysis software.

[0211] Histological section analysis; After the experiment, take the wound tissue for HE staining and immunohistochemical analysis to evaluate the tissue structure of wound healing.

[0212] Experimental setup;

[0213] There are 5 animals in each group, and 1 wound is used for the experiment on each animal to ensure sufficient sample size and reasonable experimental design.

[0214] Experimental data;

[0215] Time (days) Wound healing area of Example 2 (%) Wound healing area of Comparative Example 2 (%) 0 100.0 100.0 2 75.0 70.0 4 50.5 45.5 6 30.2 35.5 8 10.0 18.0 10 5.0 9.0 12 0.0 5.0 14 0.0 2.5

[0216] Table name; Data table of wound healing process

[0217] Summary;

[0218] By comparing the differences between the experimental group and the comparative example group during the wound healing process, the results show that the ointment in Example 2 significantly accelerated the wound healing process. The synergistic effect of the microcapsule encapsulation technology, PNIPAM, and polyacrylate in Example 2 enables the drug to adjust the release rate according to the changes in the wound environment, thereby providing the required drug support at all stages of wound healing. In the initial stage of wound healing, Example 2 shows a faster healing process, with a more obvious reduction in wound area and a significantly shortened healing time.

[0219] The ointment in Comparative Example 2 also uses the PLGA microcapsule encapsulation technology, but lacks the responsive control of PNIPAM and polyacrylate, resulting in the failure to timely adjust the drug release according to the wound state, and a slower wound healing process with an obvious lag in the healing speed. The drug release fails to effectively synchronize with the actual needs of the wound, leading to a relatively slow wound healing, especially in the later stage of wound healing, where the reduction rate of the healing area is significantly lower than that in Example 2.

[0220] The ointment in Example 2, by combining the responsive microcapsules and the matrix material, not only improves the persistence of drug release but also ensures the precise release of the drug at all stages of wound healing, significantly superior to the traditional ointment formulation.

[0221] Experiment 3; Comparative experiment on the moisturizing property of the ointment

[0222] Experimental purpose;

[0223] By measuring the moisturizing property of the ointment, this experiment compared the effects of Example 3 (PLGA microcapsules + PNIPAM + vegetable oil and glycerol matrix) and Comparative Example 3 (PLGA microcapsules + single vegetable oil matrix) to verify the advantages of the present invention in maintaining a moist wound environment.

[0224] Experimental method;

[0225] Experimental group setting;

[0226] Experimental group 1; Example 3 (PLGA microcapsules + PNIPAM + vegetable oil and glycerol matrix)

[0227] Experimental group 2; Comparative Example 3 (PLGA microcapsules + single vegetable oil matrix)

[0228] Experimental animals and wound models;

[0229] Mice were selected as experimental subjects, and a back skin scraping test was conducted with a wound diameter of about 1 cm.

[0230] An artificial wound model was used to ensure that the wound sizes were consistent and stable.

[0231] Ointment application;

[0232] The ointments prepared in Experimental group 1 and Experimental group 2 were evenly applied to the wounds of the experimental animals, 1 g each time, and continuously applied for 7 days.

[0233] Moisture measurement;

[0234] A skin hydration meter was used to regularly measure the moisture of the wounds.

[0235] Measurements were taken every 6 h, and the changes in wound moisture were recorded for 48 h.

[0236] Experimental settings;

[0237] Measurement time points: 0 h (initial), 6 h, 12 h, 24 h, 48 h. Record the changes in moisture over time and compare the moistening effects between different groups.

[0238] Experimental data;

[0239] Time (hours) Humidity of Example 3 (unit: AU) Humidity of Comparative Example 3 (unit: AU) 0 85 84 6 78 72 12 74 65 24 68 58 36 62 52 48 57 49

[0240] Table name: Comparative data table of ointment moisturizing properties

[0241] Summary;

[0242] Experimental data show that the ointment in Example 3 is significantly superior to that in Comparative Example 3 in terms of maintaining wound moisture. Over time, the moisture level in Example 3 remains at a relatively high level compared to that in Comparative Example 3, demonstrating that the combined use of vegetable oil and glycerol can effectively lock in the moisture of the wound. The moisturizing effect of a single vegetable oil matrix is relatively limited, and with the passage of time, the wound moisture level drops rapidly. The addition of glycerol increases the lubricity of the ointment and further enhances the hydration effect, keeping the wound moist and contributing to wound repair and healing.

[0243] The introduction of glycerol increases the hydrophilicity of the ointment, enabling the ointment to better retain moisture on the wound surface and form a protective film on the wound surface to prevent moisture evaporation. A moist environment can accelerate skin regeneration and reduce scar formation. In contrast, Comparative Example 3 relies only on vegetable oil and fails to effectively maintain wound moisture, so the effect in terms of maintaining moisture is poor.

[0244] Example 3 utilizes the synergistic effect of vegetable oil and glycerol, combined with the release characteristics of drugs encapsulated in PLGA microcapsules, not only improving the stability and persistence of drugs but also showing advantages in maintaining the moist environment of the wound, ensuring the stability of the hydration effect during the wound repair process.

[0245] Experiment 4; Wound temperature responsiveness comparison experiment

[0246] Experiment purpose;

[0247] This experiment mainly tests the drug release of Example 4 (PNIPAM temperature-responsive microcapsules + PLGA + vegetable oil matrix) and Comparative Example 4 (traditional microcapsules + no PNIPAM temperature-responsive material) in different temperature environments to verify the influence of temperature-responsive materials on drug release.

[0248] Experiment method;

[0249] Experimental group setting;

[0250] Experimental group 1; Example 4 (PNIPAM temperature-responsive microcapsules + PLGA + vegetable oil matrix)

[0251] Experimental group 2; Comparative Example 4 (traditional microcapsules + no PNIPAM temperature-responsive material)

[0252] Experimental sample preparation;

[0253] The ointments prepared from Example 4 and Comparative Example 4 are used, and 1 g of samples from each group are taken for testing.

[0254] Temperature regulation and drug release testing;

[0255] Apply the ointment evenly on the artificial skin model and place it in normal saline solutions at different temperatures (28°C, 35°C, 40°C, 42°C).

[0256] Take samples every 30 minutes, measure the drug concentration using high performance liquid chromatography (HPLC), continuously test for 6 hours, and observe the effect of temperature changes on drug release.

[0257] Experimental setup;

[0258] Measure the drug release rate at different temperatures and plot the release curve.

[0259] Focus on observing the release of the PNIPAM temperature-responsive material at high temperatures and compare it with traditional microcapsule ointments.

[0260]

[0261] Table name; Temperature-responsive drug release data table

[0262] Summary;

[0263] Experimental data shows that at low temperature (28°C) and normal temperature (35°C) environments, the drug release rates of Example 4 and Comparative Example 4 are relatively close, indicating that in the absence of temperature stimulation, the release trends of the two ointments are relatively similar. When the temperature increases, the drug release of Example 4 significantly accelerates, higher than that of Comparative Example 4. The phase change effect of PNIPAM appears at this moment, and the temperature triggers the rapid release of the drug, enabling the drug to quickly enter the wound surface under high temperature conditions and effectively meet the treatment needs during the inflammatory period.

[0264] PNIPAM is a typical temperature-responsive material. When the body temperature rises to its phase transition temperature, it will swell or change its structure, causing the drug encapsulated in the microcapsule to be rapidly released. When the temperature continues to rise, the structure of the outer layer of PNIPAM disintegrates, and the drug rapidly diffuses from the microcapsule. In Comparative Example 4, due to the lack of this temperature-sensitive material, its release rate does not increase significantly.

[0265] Example 4 can respond to the temperature increase at the inflammatory site, actively accelerate drug release, and provide a rapid therapeutic effect. The drug release of Comparative Example 4 is relatively fixed, and regardless of the temperature, the release rate changes little, lacking adaptability. At the initial stage of inflammation, the rapid release of the drug can effectively relieve local inflammation. When the temperature drops, the drug release rate gradually returns to the normal level, avoiding excessive release and improving the treatment accuracy of the ointment.

[0266] Although embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A lower limb wound treatment ointment based on traditional Chinese medicine, characterized in that: The composition comprises the following components by weight percentage: The drug powder mixture comprises 5-15%, polylactic acid-glycolic acid copolymer 15-25%, poly N-isopropylacrylamide 1-3%, polyacrylic acid salt 1-3%, vegetable oil 30-40%, glycerol 5-10% and deionized water 10-20%.

2. A lower limb wound treatment ointment based on traditional Chinese medicine according to claim 1, characterized in that: The medicine powder mixture comprises 30-40% of Phellodendron amurense, 20-30% of Sophora flavescens, 15-25% of Lithospermum officinale, 10-15% of Angelica sinensis and 5-10% of Lycium barbarum, and is obtained by crushing Phellodendron amurense, Sophora flavescens, Lithospermum officinale, Angelica sinensis and Lycium barbarum and then mixing them.

3. A Chinese medicine-based ointment for treating lower limb wounds according to claim 1, characterized in that: The polylactic acid-glycolic acid copolymer is prepared by condensation polymerization of lactic acid and glycolic acid.

4. A method for preparing a lower limb wound treatment ointment based on traditional Chinese medicine, according to the lower limb wound treatment ointment based on traditional Chinese medicine according to claims 1-3, characterized in that: The steps include: S1, crushing Phellodendron chinense, Sophora flavescens, Lithospermum officinale, Angelica sinensis, and Lycium barbarum into 80-120 mesh powders, and mixing them to obtain a medicinal powder mixture; S2, dissolving the drug powder mixture and polylactic acid-co-glycolic acid copolymer in an organic solvent, and preparing microcapsules by solvent evaporation method to form drug carriers; S3, mixing the microcapsules with poly (N-isopropylacrylamide) and polyacrylic acid salt, and coating them to obtain environmentally responsive microcapsules; S4, mixing vegetable oil, glycerin and deionized water, stirring at 50-70° C. for 30-60 min to form a uniform matrix; S5, adding the environmentally responsive microcapsules into the matrix and stirring for 20-50 min to obtain a uniformly dispersed ointment; S6, homogenizing and filling into a container to obtain a finished ointment.

5. The method for preparing a lower limb wound treatment ointment based on traditional Chinese medicine according to claim 4, characterized in that: In step S2, the particle size of the microcapsules is controlled to be 200-500 nm, and the drug embedding rate is 70-90%.

6. The method for preparing a lower limb wound treatment ointment based on traditional Chinese medicine according to claim 4, characterized in that: The temperature of the solvent evaporation method in step S2 is controlled at 40-60° C., the solvent evaporation process time is 1-3 hours, and the organic solvent is dichloromethane.

7. The method for preparing a lower limb wound treatment ointment based on traditional Chinese medicine according to claim 4, characterized in that: The coating thickness of poly (N-isopropylacrylamide) and polyacrylate in step S3 is 50-200 nm.

8. The method for preparing a lower limb wound treatment ointment based on traditional Chinese medicine according to claim 4, characterized in that: In step S4, the mass ratio of vegetable oil to glycerol is 3:1 to 5:1, and the stirring rate is 300-800 rpm.

9. The method for preparing a lower limb wound treatment ointment based on traditional Chinese medicine according to claim 4, characterized in that: In step S5, the stirring temperature is 25-40° C. and the stirring time is 20-60 min to ensure that the drug and the matrix are evenly mixed.

10. The method for preparing a lower limb wound treatment ointment based on traditional Chinese medicine according to claim 4, characterized in that: The homogenization treatment in step S6 is performed by using a homogenizer at 8000-15000 rpm for 3-10 min.

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