Compound traditional Chinese medicine sustained-release microcapsule, drug-loaded fabric and preparation method thereof

Abstract

This invention discloses a compound traditional Chinese medicine sustained-release microcapsule, a drug-loaded fabric, and their preparation method, belonging to the field of microcapsule drug delivery technology. The preparation method of the compound traditional Chinese medicine sustained-release microcapsule involves successfully encapsulating water-soluble compound traditional Chinese medicine Chai Gui Xiao Ji granules within a hydrophobic polycaprolactone wall material, resulting in a compound traditional Chinese medicine sustained-release microcapsule with uniform particle size, good dispersibility, and a core-shell structure. Further, the compound traditional Chinese medicine sustained-release microcapsule is compounded with an aqueous finishing agent and fixed onto the surface of a fabric to obtain a drug-loaded fabric. The drug-loaded fabric of this invention achieves effective regulation of drug release, further prolonging the drug release cycle. Simultaneously, the drug-loaded fabric possesses good flexibility and extensibility, adapting to human activity needs and providing excellent wearing comfort, thus achieving a balance between drug sustained-release function and basic fabric performance.

Description

Technical Field

[0001] This invention relates to the field of microcapsule drug delivery technology, and in particular to a compound traditional Chinese medicine sustained-release microcapsule, a drug-loaded fabric, and a method for preparing the same. Background Technology

[0002] Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxic reaction in cancer treatment, characterized by its long-term, localized, and diverse clinical manifestations. In the field of traditional Chinese medicine, the compound herbal formula Chai Gui Xiao Ji Fang, based on the "principal, assistant, adjuvant, and guide" theory, has been proven to alleviate tumor-related neuropathological changes and has shown potential in improving neurological sequelae in clinical practice (Sun QX, Wang Q, Fang LQ, et al. Iron oxide / lipid nanoparticles loaded with traditional Chinese medicine CGXJF constituents inhibit pancreatic cancer progression. Rare Metals, 2025, (prepublish): 1-16.). However, this compound is currently mainly administered orally, which has drawbacks such as a bitter taste and potential for gastrointestinal discomfort, leading to low patient compliance. Furthermore, the drug undergoes first-pass absorption in the liver after oral administration, resulting in decreased bioavailability and difficulty in consistently achieving therapeutic effects.

[0003] Patent application CN113101879 A discloses a method for preparing microcapsules of Isatis indigotica volatile oil. It employs a chemical cross-linking grafting method to treat fabrics with microcapsules, enabling the microcapsules to achieve good adhesion and wash resistance, and exhibiting highly efficient, broad-spectrum, and safe antibacterial properties. However, this method targets a single active ingredient and struggles to achieve balanced encapsulation and release of multiple components with different properties in a compound formulation.

[0004] Therefore, providing a novel drug delivery system for compound traditional Chinese medicines that enables convenient, continuous, and non-invasive drug administration is of vital importance for improving the convenience of treatment, enhancing the patient's medication experience, and ensuring the stability of therapeutic efficacy. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a compound traditional Chinese medicine sustained-release microcapsule, a drug-loaded fabric, and a method for preparing the same. The microcapsules and fabric of this invention enable the assembly and slow release of the compound traditional Chinese medicine, while the fabric also provides wearing comfort.

[0006] The technical solution of this invention is as follows: The first aspect of this invention protects a method for preparing compound traditional Chinese medicine sustained-release microcapsules, comprising the following steps: S1. At temperature T, disperse the Chai Gui Xiao Ji granules into an aqueous solution of stabilizer I, and cool it to room temperature to obtain the inner aqueous phase; S2. Disperse the wall material and emulsifier into the oil, stir, and obtain the oil phase; S3. Add the internal aqueous phase to the oil phase and emulsify to obtain a primary emulsion; S4. Add the primary emulsion to the external aqueous phase and emulsify to obtain a secondary emulsion; S5. Remove the oil from the compound emulsion to obtain a microcapsule emulsion. Centrifuge to collect the precipitate, wash, and dry to obtain compound traditional Chinese medicine sustained-release microcapsules.

[0007] Preferably, in step S1, the stabilizer I includes at least one of polyvinyl alcohol and sodium alginate; The temperature T is 40~60℃; The room temperature is 20~30℃; The content of Chai Gui Xiao Ji Granules in the internal aqueous phase is 10~80mg / mL; The content of stabilizer I in the internal aqueous phase is 1~1.5wt%.

[0008] Preferably, in step S2, the wall material comprises polycaprolactone; The emulsifier includes at least one of Span-80 and Span-60; The oil agent includes dichloromethane; The stirring temperature is 25~40℃, and the stirring time is 0.5~1.5h.

[0009] Preferably, in step S2, the content of wall material in the oil phase is 4-6 wt%; and the content of emulsifier in the oil phase is 5-7 wt%.

[0010] Preferably, in step S3, the mass ratio of the internal aqueous phase to the oil phase is 1:(3~4). The internal aqueous phase was added to the oil phase under ice bath and homogenization conditions of 8000~10000 r / min; The emulsification time is 3-5 minutes.

[0011] Preferably, in step S4, the external aqueous phase is an aqueous solution of stabilizer II; The stabilizer II includes polyvinyl alcohol; The content of stabilizer II in the external aqueous phase is 2~2.5 wt%; The mass ratio of the primary emulsion to the external aqueous phase is 1:(3~4). The primary emulsion was added to the external aqueous phase under homogenization at 6000~8000 r / min; The emulsification time is 3-5 minutes; In step S5, the centrifugation speed is 6500~7500 rpm. The drying time is 40-55 hours.

[0012] The second aspect of this invention protects a compound traditional Chinese medicine sustained-release microcapsule prepared by the preparation method described in the first aspect.

[0013] A third aspect of this invention protects a method for preparing a drug-loaded fabric, comprising the following steps: (1) The compound Chinese medicine sustained-release microcapsule emulsion was evenly dispersed into the aqueous solution of the finishing agent to obtain the coating solution; (2) Immerse the fabric completely in the coating solution; after soaking and stirring at room temperature, pass the fabric through rollers to remove excess coating solution; bake at low temperature and dry to obtain drug-loaded fabric; In step (1), the compound traditional Chinese medicine sustained-release microcapsule emulsion is obtained by dispersing compound traditional Chinese medicine sustained-release microcapsules in water; The compound traditional Chinese medicine sustained-release microcapsules are compound traditional Chinese medicine sustained-release microcapsules prepared by the preparation method described in the first aspect, and / or compound traditional Chinese medicine sustained-release microcapsules described in the second aspect.

[0014] Preferably, in step (1), the content of compound traditional Chinese medicine sustained-release microcapsules in the coating solution is 1.5~2.5 wt%; The coating solution contains a finishing agent content of 4-8 wt%; The finishing agent includes polyurethane; In step (2), the fabric includes at least one of cotton, cotton-polyester blend, and polyester. The room temperature is 20~30℃; The stirring time is 25-35 minutes; The low-temperature baking temperature is 45~55℃, and the time is 15~25min; The fabric has a roll-off rate of 65-75%.

[0015] The fourth aspect of this invention protects the drug-loaded fabric prepared by the preparation method described in the third aspect.

[0016] The present invention has the following beneficial effects: This invention successfully encapsulates water-soluble compound traditional Chinese medicine Chai Gui Xiao Ji granules within a hydrophobic polycaprolactone wall material, producing compound traditional Chinese medicine sustained-release microcapsules with uniform particle size (average particle size of approximately 800 nm), good dispersibility, and a core-shell structure. Furthermore, the drug release curve of the microcapsules exhibits a typical biphasic characteristic of initial burst release followed by a gradual release, demonstrating excellent sustained-release performance.

[0017] This invention further combines compound traditional Chinese medicine sustained-release microcapsules with an aqueous finishing agent, fixing them onto the surface of a fabric to obtain a drug-loaded fabric. The drug-loaded fabric of this invention achieves effective regulation of drug release, further prolonging the drug release cycle, with the final cumulative release rate remaining stable at 42%. This indicates that the composite system composed of microcapsules and fabric forms an effective drug release barrier, capable of delaying and stabilizing the drug release rate, demonstrating the potential for constructing a long-acting sustained-release system. Simultaneously, the drug-loaded fabric also maintains excellent basic performance characteristics, with an air permeability exceeding 190 mm / s and a moisture permeability exceeding 200 g / (m²). 2 It has a breaking elongation of up to 110%, good flexibility and extensibility, and can adapt to the needs of human activity, providing good wearing comfort for human wearers, and achieving a balance between drug sustained release function and basic fabric wearing performance. Attached Figure Description

[0018] Figure 1 The figure shows the particle size determination results of CGXJF1, CGXJF2 and Comparative Example 1 compound traditional Chinese medicine sustained-release microcapsules.

[0019] Figure 2 Photographs showing the appearance of the primary emulsions in Example 1 and Comparative Example 1.

[0020] Figure 3 The results of infrared absorption spectroscopy measurements for Chai Gui Xiao Ji Granules, CGXJF1, and CGXJF2 are shown.

[0021] Figure 4 The graph shows the results of air permeability testing of drug-loaded fabrics with WPU of 5%, WPU of 7.5%, and Comparative Example 3.

[0022] Figure 5 The graph shows the moisture permeability test results for drug-loaded fabrics with WPU of 5%, WPU of 7.5%, and Comparative Example 3.

[0023] Figure 6 The graph shows the strain and stress measurement results of drug-loaded fabrics with WPU of 5%, WPU of 7.5%, and Comparative Example 3.

[0024] Figure 7 The graph shows the cumulative drug release results for CGXJF1 and WPU 7.5%. Detailed Implementation

[0025] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided below.

[0026] A method for preparing compound traditional Chinese medicine sustained-release microcapsules includes the following steps: S1. At temperature T, disperse the Chai Gui Xiao Ji granules into an aqueous solution of stabilizer I, and cool it to room temperature to obtain the inner aqueous phase; S2. Disperse the wall material and emulsifier into the oil, stir, and obtain the oil phase; S3. Add the internal aqueous phase to the oil phase and emulsify to obtain a primary emulsion; S4. Add the primary emulsion to the external aqueous phase and emulsify to obtain a secondary emulsion; S5. Remove the oil from the compound emulsion to obtain a microcapsule emulsion. Centrifuge to collect the precipitate, wash, and dry to obtain compound traditional Chinese medicine sustained-release microcapsules.

[0027] Preferably, the stabilizer I is polyvinyl alcohol, and the aqueous solution of stabilizer I is an aqueous solution of polyvinyl alcohol. Preferably, the external aqueous phase is an aqueous solution of polyvinyl alcohol.

[0028] The above-mentioned polyvinyl alcohol aqueous solution is obtained by the following method: polyvinyl alcohol is dissolved in deionized water and stirred at 90°C for 1 to 1.5 hours until completely dissolved to obtain a polyvinyl alcohol aqueous solution.

[0029] Preferably, the wall material is polycaprolactone.

[0030] Polycaprolactone can be stably dispersed in the oil-based dichloromethane, forming an effective physical barrier against the water-soluble Chai Gui Xiao Ji granules. During the subsequent volatilization of the oil, polycaprolactone undergoes phase separation and precipitation at the oil-water interface due to the decrease in solubility. With its excellent film-forming properties, it tightly encapsulates the inner aqueous phase, ultimately forming a regular and stable core-shell structured microcapsule.

[0031] During the drug release phase, the hydrophobic framework and semi-permeability of polycaprolactone constitute a dual control mechanism. Initially, a small amount of drug adsorbed on the surface of the microcapsule is rapidly released. Subsequently, through the synergistic effect of the slow hydrolysis and erosion of the polymer chain and the diffusion of drug molecules in the polymer matrix, the continuous and gradual release of the drug inside the capsule is achieved.

[0032] Furthermore, the flexibility and mechanical stability of polycaprolactone-based microcapsules endow them with excellent deformation resistance, making them highly compatible with the polyurethane finishing agent in the coating solution. Under the adhesive effect of the finishing agent, the microcapsules can firmly adhere to the fabric fibers without clogging the fiber gaps, thus fundamentally ensuring that the drug-loaded fabric can achieve both long-lasting sustained release and excellent breathability and wearing comfort.

[0033] In some embodiments, in step S2, the content of the wall material in the oil phase is 4-6 wt%.

[0034] Understandably, the amount of polycaprolactone added should not be too high or too low. If the amount of polycaprolactone added is too high, it will be difficult to disperse into small droplets during homogenization emulsification in the microcapsule preparation process. This results in excessively large droplet sizes in the primary and secondary emulsions, leading to increased microcapsule particle size and uneven distribution. Simultaneously, it will cause the microcapsule walls to become too thick, thus hindering the diffusion of the compound traditional Chinese medicine, resulting in an excessively long drug release period, and potentially preventing the drug from being released from the capsule.

[0035] If the amount of polycaprolactone added is too low, the microcapsule walls will be too thin, and may even contain holes or defects, resulting in a decrease in encapsulation efficiency. Furthermore, excessively thin capsule walls cannot effectively prevent drug release, causing the drug to be released in a very short time, failing to achieve a sustained-release effect. In addition, insufficient polycaprolactone addition will also lead to insufficient mechanical strength of the microcapsules, making them very prone to breakage during subsequent centrifugation, washing, drying, and bonding with fabrics, resulting in premature drug leakage.

[0036] In some embodiments, the method for removing the oil from the re-emulsion is as follows: the re-emulsion is placed in a rotary evaporator and the oil is removed at a speed of 30-100 r / min and at a temperature of 20-30°C.

[0037] A method for preparing a drug-loaded fabric includes the following steps: (1) The compound Chinese medicine sustained-release microcapsule emulsion was evenly dispersed into the aqueous solution of the finishing agent to obtain the coating solution; (2) Immerse the fabric completely in the coating solution; after soaking and stirring at room temperature, pass the fabric through rollers to remove excess coating solution; bake at low temperature and dry to obtain drug-loaded fabric.

[0038] Low-temperature baking enables polyurethane to form a film, thereby allowing the microcapsules to adhere firmly to the fabric fibers.

[0039] In some embodiments, the fabric is cotton. Preferably, the cotton fabric is a plain knit fabric.

[0040] In some embodiments, step (2) of drying includes hanging the baked fabric in a dry and ventilated condition for 12 hours to dry.

[0041] In some embodiments, the coating solution contains a finishing agent content of 4-8 wt%. Preferably, the finishing agent is polyurethane.

[0042] Understandably, the amount of polyurethane added should not be too high or too low. If the amount of polyurethane added is too high, the polyurethane film will block the natural gaps between the fibers, negatively affecting the air permeability and moisture permeability of the drug-loaded fabric. At the same time, excessive polyurethane will over-encapsulate the microcapsules, thereby hindering drug release.

[0043] If the amount of polyurethane added is too low, an effective cross-linking network cannot be formed between the microcapsules and the fabric fibers. When the fabric is subjected to friction or stretching during daily wear, a large number of microcapsules will fall off, and the effective drug loading on the fabric surface will become uneven, failing to provide a stable and predictable therapeutic effect.

[0044] The raw materials used in the following embodiments and comparative examples of the present invention can all be purchased.

[0045] Example 1 A method for preparing compound traditional Chinese medicine sustained-release microcapsules includes the following steps: S1. Dissolve polyvinyl alcohol in deionized water and stir at 90°C for 1.5 h to dissolve. Cool to 50°C to obtain a polyvinyl alcohol aqueous solution. Disperse Chai Gui Xiao Ji granules into the polyvinyl alcohol aqueous solution and cool to room temperature to obtain an inner aqueous phase. In the inner aqueous phase, the content of Chai Gui Xiao Ji granules is 20 mg / mL and the mass content of polyvinyl alcohol is 1.5%.

[0046] S2. Disperse polycaprolactone and Span-80 emulsifier in dichloromethane and stir at 40°C for 1 hour to obtain an oil phase; in the oil phase: the mass content of polycaprolactone is 5% and the mass content of Span-80 emulsifier is 6%.

[0047] S3. Under ice bath and homogenization conditions of 8000 r / min, the internal aqueous phase is added to the oil phase at a mass ratio of 1:3, and emulsification is carried out for 4 min to obtain the primary emulsion.

[0048] S4. Dissolve polyvinyl alcohol in deionized water and stir at 90°C for 1.5 h until dissolved. Cool to room temperature to obtain an external aqueous phase. The mass content of polyvinyl alcohol in the external aqueous phase is 2%.

[0049] S5. Add the primary emulsion to the external aqueous phase at a mass ratio of 1:3, and emulsify at 6000 r / min for 3 min to obtain the secondary emulsion.

[0050] S6. Place the compound emulsion in a rotary evaporator at 100 r / min and 25°C to remove dichloromethane and obtain a microcapsule emulsion; centrifuge three times at 7000 rpm to remove the supernatant, and then put the collected precipitate into a freeze dryer for 48 hours to obtain compound traditional Chinese medicine sustained-release microcapsules (abbreviated as CGXJF1).

[0051] Example 2 A method for preparing compound traditional Chinese medicine sustained-release microcapsules includes the following steps: S1. Dissolve polyvinyl alcohol in deionized water and stir at 90°C for 1.5 h to dissolve. Cool to 50°C to obtain a polyvinyl alcohol aqueous solution. Disperse Chai Gui Xiao Ji granules into the polyvinyl alcohol aqueous solution and cool to room temperature to obtain an inner aqueous phase. In the inner aqueous phase, the content of Chai Gui Xiao Ji granules is 50 mg / mL and the mass content of polyvinyl alcohol is 1.5%.

[0052] S2. Polycaprolactone and Span-80 emulsifier are dispersed in dichloromethane and stirred at 40°C for 1 hour to obtain an oil phase; in the oil phase: the mass content of polycaprolactone is 5% and the mass content of Span-80 emulsifier is 6%.

[0053] S3. Under ice bath and homogenization conditions of 8000 r / min, the internal aqueous phase is added to the oil phase at a mass ratio of 1:3, and emulsification is carried out for 4 min to obtain the primary emulsion.

[0054] S4. Dissolve polyvinyl alcohol in deionized water and stir at 90°C for 1.5 h until dissolved. Cool to room temperature to obtain an external aqueous phase. The mass content of polyvinyl alcohol in the external aqueous phase is 2%.

[0055] S5. Add the primary emulsion to the external aqueous phase at a mass ratio of 1:3, and emulsify at 6000 r / min for 3 min to obtain the secondary emulsion.

[0056] S6. Place the compound emulsion in a rotary evaporator at 100 r / min and 25°C to remove dichloromethane and obtain a microcapsule emulsion; centrifuge three times at 7000 rpm to remove the supernatant, and then put the collected precipitate into a freeze dryer for 48 hours to obtain compound traditional Chinese medicine sustained-release microcapsules (abbreviated as CGXJF2).

[0057] Example 3 A method for preparing a drug-loaded fabric includes the following steps: (1) The compound Chinese medicine sustained-release microcapsules prepared in Example 1 were dispersed in water to obtain a microcapsule emulsion. The microcapsule emulsion was uniformly dispersed in a polyurethane aqueous solution to obtain a coating solution. The coating solution contained 2 wt% compound Chinese medicine sustained-release microcapsules and 5 wt% polyurethane.

[0058] (2) Immerse the cotton fabric completely in the coating solution to ensure full wetting; after soaking and stirring at room temperature for 30 minutes, pass the fabric through the rollers and set the pick-up rate to 70% to remove excess coating solution; then bake at 50°C for 20 minutes, and hang it in a dry and ventilated environment for 12 hours to dry to obtain drug-loaded fabric (abbreviated as WPU5%).

[0059] Example 4 A method for preparing a drug-loaded fabric includes the following steps: (1) The compound Chinese medicine sustained-release microcapsules prepared in Example 1 were dispersed in water to obtain a microcapsule emulsion. The microcapsule emulsion was uniformly dispersed in a polyurethane aqueous solution to obtain a coating solution. The coating solution contained 2 wt% compound Chinese medicine sustained-release microcapsules and 7.5 wt% polyurethane.

[0060] (2) Immerse the cotton fabric completely in the coating solution to ensure full wetting; after soaking and stirring at room temperature for 30 minutes, pass the fabric through the rollers and set the pick-up rate to 70% to remove excess coating solution; then bake at 50°C for 20 minutes, and hang it in a dry and ventilated place for 12 hours to dry to obtain drug-loaded fabric (abbreviated as WPU7.5%).

[0061] Comparative Example 1 A method for preparing compound traditional Chinese medicine sustained-release microcapsules is basically the same as that in Example 1, except that in step S2, the mass content of polycaprolactone in the oil phase is 2.5%.

[0062] Comparative Example 2 A method for preparing compound traditional Chinese medicine sustained-release microcapsules is basically the same as that in Example 1, except that in step S3, the mass ratio of the internal aqueous phase to the oil phase is 1:2.

[0063] Comparative Example 3 A method for preparing a drug-loaded fabric is basically the same as that in Example 3, except that in step (1), the content of polyurethane in the coating solution is 10wt%.

[0064] Test example: Test Example 1 The particle size distribution of CGXJF1 prepared in Example 1, CGXJF2 prepared in Example 2, and microcapsules prepared in Comparative Example 1 were determined using a Malvern laser particle size analyzer. Deionized water was used as the dispersant, and each sample was measured in triplicate, with the average value taken. The particle size distribution maps of CGXJF1, CGXJF2, and the microcapsules of Comparative Example 1 are shown below. Figure 1 As shown.

[0065] Combination Figure 1 It can be seen that the peak shapes of CGXJF1 prepared in Example 1 and CGXJF2 prepared in Example 2 are both concentrated, single, narrow peaks. The particle size of CGXJF1 is smaller than that of CGXJF2 because the content of Chai Gui Xiao Ji granules in CGXJF1 is less than that in CGXJF2. In contrast, the particle size distribution of the microcapsules prepared in Comparative Example 1 is dispersed and shows bimodal peaks. This is because the amount of polycaprolactone added in Comparative Example 1 is too small, resulting in unstable and fragile microcapsules with significantly reduced overall strength.

[0066] Test Example 2 Figure 2 These are photographs showing the appearance of the primary emulsions prepared in Example 1 and Comparative Example 1. (Combined with...) Figure 2 It can be seen that the primary emulsion system of Example 1 is uniform and without stratification, while the primary emulsion of Comparative Example 1, which has too little polycaprolactone added, shows stratification, indicating that the inner aqueous phase is not completely emulsified. This is because when preparing compound traditional Chinese medicine sustained-release microcapsules using the method of this invention, the appropriate ratio of the inner aqueous phase to the oil phase can improve the interfacial adsorption efficiency of the emulsifier, thereby more stably encapsulating the inner aqueous phase and obtaining a primary emulsion with better stability.

[0067] Test Example 3 The infrared absorption spectra of the core materials Chai Gui Xiao Ji Granules, CGXJF1, and CGXJF2 were measured using Fourier transform infrared spectroscopy. The results are as follows: Figure 3 As shown.

[0068] Depend on Figure 3 It can be seen that Chai Gui Xiao Ji Granules are at 3269cm -1 A broad OH peak (drug functional group) is present at 3269 cm⁻¹, but... -1 The broad OH peak at 1725 cm⁻¹ weakened to almost disappearing in the spectra of CGXJF1 and CGXJF2, and the peaks of CGXJF1 and CGXJF2 at 1725 cm⁻¹ were also observed. -1 The presence of a strong absorption peak for polycaprolactone in the wall material confirms that in both of the above embodiments, the Chai Gui Xiao Ji granules have been successfully encapsulated in microcapsules.

[0069] Test Example 4 The air permeability of the drug-loaded fabrics in Examples 3, 4, and Comparative Example 3 was determined using a fabric air permeability meter. The WPU (5%) fabric prepared in Example 3, the WPU (7.5%) fabric prepared in Example 4, and the fabric prepared in Comparative Example 3 were each measured three times, and the average value was taken. The results are as follows: Figure 4 As shown.

[0070] Combination Figure 4 It can be seen that after treatment with polyurethane aqueous solution, the air permeability of the fabric first decreases significantly and then tends to level off as the concentration of polyurethane aqueous solution increases. The air permeability of the drug-loaded fabric can all reach above 190.0 mm / s, which can meet the skin comfort and breathability requirements after being applied to the human body, with Example 3 showing better air permeability.

[0071] Test Example 5 The moisture permeability of the drug-loaded fabrics in Examples 3, 4, and Comparative Example 3 was determined using a computerized fabric moisture permeability meter. The moisture permeability test was conducted according to GB / T 12704.2-2009 standard (38℃, 50% RH). The WPU 5%, WPU 7.5%, and Comparative Example 3 fabrics were measured four times each, and the average value was taken. The results are as follows: Figure 5 As shown.

[0072] Combination Figure 5It can be seen that the moisture permeability of the fabric in Example 4 is slightly greater than that in Example 3. This is because the hydrogen bond network formed by the hydrophilic groups in the polyurethane aqueous solution molecular chain constructs a continuous water vapor transport channel, which synergistically promotes the diffusion of water molecules. The moisture permeability of the drug-loaded fabric in Comparative Example 3 is significantly lower than that in Examples 3 and 4. This is because the excessive polyurethane water causes blockage of the diffusion path, which is not conducive to the diffusion of water molecules.

[0073] Combination Figure 4 and 5 It can be seen that the drug-loaded fabrics prepared in Examples 3 and 4 of the present invention have better air permeability and moisture permeability, while the drug-loaded fabric prepared in Comparative Example 3 has better air permeability, but poorer moisture permeability.

[0074] Test Example 6 The breaking strength and elongation at break of the drug-loaded fabrics of Examples 3, 4, and Comparative Example 3 were tested using an electronic fabric tensile testing machine. Fabrics with WPU 5%, WPU 7.5%, and Comparative Example 3 were cut into 6×6 mm pieces, and each was tested once. The results are as follows: Figure 6 As shown.

[0075] Combination Figure 6 It can be seen that the drug-loaded fabric (WPU 7.5%) of Example 4 can provide the maximum elongation and can be used for medical dressings, patches and other products that need to be in contact with the skin, while the fabric of Comparative Example 3 has the worst elasticity due to the excessive use of water-based polyurethane solution for finishing.

[0076] Test Example 7 Take 2 mg of CGXJF1 from Example 1, reconstitute it with 1.5 mL of deionized water, place it in a 10 cm dialysis bag and seal it with a dialysis clamp. Then, immerse it in a 50 mL beaker containing 20 mL of PBS release medium to begin the release experiment. Place the beaker under constant temperature magnetic stirring at 100 r / min and 37 °C for release. Every so often, take 4 mL of solution from the beaker and add 4 mL of sustained-release solution to keep the total release medium in the system constant. Plot the cumulative drug release curve of CGXJF1.

[0077] The drug-loaded fabric (WPU 7.5%) prepared in Example 4 was cut into 1 cm × 1 cm samples and placed in a dialysis bag containing 3 mL of deionized water. Both ends were sealed with dialysis clamps. The bag was then placed in a 100 mL beaker, and 80 mL of PBS (the release medium) was added to bring the total dialysis medium to 80 mL. The beaker was placed under constant temperature magnetic stirring at 100 r / min and 37 °C for release. Every so often, 4.5 mL of solution was removed from the beaker, and 4.5 mL of PBS solution was added simultaneously to maintain a constant total release medium. A cumulative drug release curve for the WPU 7.5% fabric was plotted.

[0078] Formula for calculating cumulative drug release rate: In the formula: Q(t) is the cumulative drug release rate, %; C(t) is the concentration of the drug in the release medium at the last sampling time point, μg·mL. -1 V0 represents the total volume of the release medium, in mL; C(i) represents the concentration of the drug in the release medium at the i-th sampling time point, in μg·mL. -1 Vs is the test solution taken at the i-th time point, in mL; m durg The total mass of the drug in the microcapsules is expressed in mg.

[0079] Depend on Figure 7 It can be seen that the drug release curve of CCXJF1 exhibits a biphasic release characteristic, with a burst release phase within 0-8 hours, followed by a significant decrease in the release rate, and a slow and gradual release within 8-25 hours. This means that the compound traditional Chinese medicine sustained-release microcapsules prepared using the method of this invention can achieve a sustained-release effect, and this release mode is closely related to the hydrophobic crystallization properties of polycaprolactone as the wall material and the preparation method of this invention.

[0080] Furthermore, the release period of the drug-loaded fabric WPU7.5% prepared by the method of the present invention is nearly twice as long as that of CGXJF1, and the final cumulative release rate (42%) is significantly reduced to half that of the CGXJF1 system. This indicates that in the drug-loaded fabric prepared by the present invention, the composite matrix composed of cotton fabric and polyurethane aqueous solution creates a barrier to drug release and retains part of the drug, which can provide a more promising delivery system for applications requiring sustained and stable drug delivery.

[0081] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for preparing compound traditional Chinese medicine sustained-release microcapsules, characterized in that, Includes the following steps: S1. At temperature T, disperse the Chai Gui Xiao Ji granules into an aqueous solution of stabilizer I, and cool it to room temperature to obtain the inner aqueous phase; S2. Disperse the wall material and emulsifier into the oil, stir, and obtain the oil phase; S3. Add the internal aqueous phase to the oil phase and emulsify to obtain a primary emulsion; S4. Add the primary emulsion to the external aqueous phase and emulsify to obtain a secondary emulsion; S5. Remove the oil from the compound emulsion to obtain a microcapsule emulsion. Centrifuge to collect the precipitate, wash, and dry to obtain compound traditional Chinese medicine sustained-release microcapsules.

2. The preparation method according to claim 1, characterized in that, In step S1, the stabilizer I includes at least one of polyvinyl alcohol and sodium alginate; The temperature T is 40~60℃; The room temperature is 20~30℃; The content of Chai Gui Xiao Ji Granules in the internal aqueous phase is 10~80mg / mL; The content of stabilizer I in the internal aqueous phase is 1~1.5wt%.

3. The preparation method according to claim 1, characterized in that, In step S2, the wall material includes polycaprolactone; The emulsifier includes at least one of Span-80 and Span-60; The oil agent includes dichloromethane; The stirring temperature is 25~40℃, and the stirring time is 0.5~1.5h.

4. The preparation method according to claim 1, characterized in that, In step S2, the content of wall material in the oil phase is 4-6 wt%; the content of emulsifier in the oil phase is 5-7 wt%.

5. The preparation method according to claim 1, characterized in that, In step S3, the mass ratio of the internal aqueous phase to the oil phase is 1:(3~4). The internal aqueous phase was added to the oil phase under ice bath and homogenization conditions of 8000~10000 r / min; The emulsification time is 3-5 minutes.

6. The preparation method according to claim 1, characterized in that, In step S4, the external aqueous phase is an aqueous solution of stabilizer II; The stabilizer II includes polyvinyl alcohol; The content of stabilizer II in the external aqueous phase is 2~2.5 wt%; The mass ratio of the primary emulsion to the external aqueous phase is 1:(3~4). The primary emulsion was added to the external aqueous phase under homogenization at 6000~8000 r / min; The emulsification time is 3-5 minutes; In step S5, the centrifugation speed is 6500~7500 rpm. The drying time is 40-55 hours.

7. A compound traditional Chinese medicine sustained-release microcapsule prepared by the preparation method according to any one of claims 1 to 6.

8. A method for preparing a drug-loaded fabric, characterized in that, Includes the following steps: (1) The compound Chinese medicine sustained-release microcapsule emulsion was evenly dispersed into the aqueous solution of the finishing agent to obtain the coating solution; (2) Immerse the fabric completely in the coating solution; after soaking and stirring at room temperature, pass the fabric through rollers to remove excess coating solution; The drug-loaded fabric is obtained by low-temperature baking and air drying. In step (1), the compound traditional Chinese medicine sustained-release microcapsule emulsion is obtained by dispersing compound traditional Chinese medicine sustained-release microcapsules in water; The compound traditional Chinese medicine sustained-release microcapsule is the compound traditional Chinese medicine sustained-release microcapsule prepared by the preparation method described in any one of claims 1 to 6, and / or the compound traditional Chinese medicine sustained-release microcapsule described in claim 7.

9. The preparation method according to claim 8, characterized in that, In step (1), the content of compound traditional Chinese medicine sustained-release microcapsules in the coating solution is 1.5~2.5 wt%; The coating solution contains a finishing agent content of 4-8 wt%; The finishing agent includes polyurethane; In step (2), the fabric includes at least one of cotton, cotton-polyester blend, and polyester. The room temperature is 20~30℃; The stirring time is 25-35 minutes; The low-temperature baking temperature is 45~55℃, and the time is 15~25min; The fabric has a roll-off rate of 65-75%.

10. A drug-loaded fabric prepared by the method according to any one of claims 8 to 9.

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