Microcapsule wound dressing containing cannabidiol and preparation method thereof

Abstract

The invention provides a microcapsule wound dressing containing cannabidiol and a preparation method of the microcapsule wound dressing. The microcapsule wound dressing comprises polyurethane foam and functional microcapsules dispersed in the polyurethane foam. The functional microcapsule comprises a microcapsule matrix and cannabidiol located in the microcapsule matrix. The microcapsule matrix is urea resin. The microcapsule wound dressing has a stable structure in a dry environment, and when the microcapsule wound dressing is in contact with liquid such as blood, tissue fluid and the like, the urea-formaldehyde resin can be broken to release cannabidiol, so that wound healing is promoted. Meanwhile, the polyurethane foam can absorb wound exudate, the wound environment is kept stable, and wound healing is promoted. The microcapsule wound dressing is suitable for chronic wound nursing, such as diabetic foot ulcer, bedsore and the like.

Description

Technical Field

[0001] This invention belongs to the field of wound dressing technology, specifically relating to a microcapsule wound dressing containing cannabidiol and its preparation method. Background Technology

[0002] Chronic wounds (such as diabetic foot ulcers and pressure sores) generally present with problems such as long healing periods, susceptibility to infection, and difficulty in managing exudate due to issues like impaired local blood circulation, weakened immunity, and persistent inflammation. Currently, commonly used wound dressings mainly include hydrocolloid dressings and alginate dressings. While these can achieve basic functions such as exudate absorption and maintaining a moist wound environment, they lack the ability to actively promote healing and are insufficient to address the problems of prolonged inflammation and slow tissue repair in chronic wounds.

[0003] Therefore, existing wound dressings need to be improved. Summary of the Invention

[0004] The purpose of this invention is to provide a wound dressing that combines the functions of precise microcapsule release, efficient exudate management, and stable performance of active ingredients, in order to solve the technical problems of long healing cycles and difficult nursing care for chronic wounds.

[0005] A microcapsule wound dressing containing cannabidiol includes a polyurethane foam and functional microcapsules dispersed in the polyurethane foam; the functional microcapsules include a urea-formaldehyde resin microcapsule matrix and cannabidiol located inside the microcapsule matrix; the functional microcapsules account for 5%-15% of the mass of the polyurethane foam.

[0006] Optionally, the raw materials for the urea-formaldehyde resin microcapsule matrix include urea and formaldehyde, wherein the molar ratio of urea to formaldehyde is 1:1.5-2.0.

[0007] Optionally, the raw material of the urea-formaldehyde resin microcapsule matrix further includes a modifier, wherein the modifier is polyvinyl alcohol, and the amount of polyvinyl alcohol added is 5%-10% of the mass of the urea.

[0008] Optionally, the cannabidiol accounts for 20%-40% of the mass of the functional microcapsule.

[0009] Optionally, the wall thickness of the urea-formaldehyde resin microcapsule matrix is ​​0.5-2 μm, and the particle size of the functional microcapsules is 5-20 μm.

[0010] Optionally, the raw materials for the polyurethane foam include polyether polyol and isocyanate, wherein the NCO / OH molar ratio of the isocyanate to the polyether polyol is 1.05-1.15.

[0011] Optionally, the exudate absorption capacity of the polyurethane foam is 10-15 times its own mass.

[0012] Optionally, the CBD release rate of the functional microcapsules is: ≥60% after 24 hours and ≥90% after 72 hours at pH 7.0.

[0013] A method for preparing the above-mentioned microcapsule wound dressing containing cannabidiol includes the following steps: S101: Preparation of cannabidiol emulsion: Mix cannabidiol, emulsifier and deionized water, and stir to form an emulsion; S102: In-situ polymerization preparation of functional microcapsules: Urea was added to the emulsion, the pH was adjusted and formaldehyde was added dropwise, the polymerization was carried out under heat, a modifier was added, and the reaction was completed and the microcapsules were separated and dried to obtain functional microcapsules. S103: Composite preparation of dressing: Polyether polyol, isocyanate, foaming agent and catalyst are mixed, functional microcapsules are added, and after stirring, foaming and curing are carried out to obtain microcapsule wound dressing.

[0014] Optionally, in S101, the emulsifier is Tween 80, and the amount added is 10-30% of the mass of cannabidiol; In S101, the stirring speed is 3000-5000 r / min, and the stirring time is 30-60 min; In S102, the polymerization temperature is 60-70℃ and the polymerization time is 2-4h; In S103, the foaming and curing temperature is 60-80℃, and the curing time is 12-24h; In S103, the foaming agent is n-pentane, and the amount added is 5-10% of the mass of the polyether polyol; In S103, the catalyst is triethylenediamine, and the amount added is 0.5-1% of the mass of the polyether polyol.

[0015] Beneficial effects In this invention, urea-formaldehyde resin microcapsules are combined with polyurethane foam. Through the synergistic design of microcapsules responding to release active ingredients and foam matrix managing the wound environment, the technical problems of poor stability of cannabidiol, low controllability of release, and difficulty in managing exudate from chronic wounds are solved. The resulting wound dressing can combine the precise response and release of microcapsules, efficient exudate management, and stable performance of active ingredients, thus solving the technical problems of long healing cycles and high nursing difficulty of chronic wounds. Detailed Implementation

[0016] For chronic wounds, while commonly used wound dressings can achieve basic functions such as absorbing exudate and maintaining a moist environment in the wound, they lack the effect of actively promoting healing and are unable to solve the problems of prolonged inflammation and slow tissue repair in chronic wounds.

[0017] Cannabidiol (CBD), a natural active ingredient with anti-inflammatory, antibacterial, and cell proliferation and angiogenesis-promoting properties, has shown significant potential in wound healing. However, CBD suffers from technical limitations such as poor stability (easily oxidized and photodegraded), low water solubility (difficult to release evenly at the wound site), and low bioavailability (easily blocked by the stratum corneum when applied directly), which restrict its application in wound dressings.

[0018] While existing microcapsule technology can encapsulate active ingredients to improve stability, commonly used microcapsule matrices (such as gelatin and gum arabic) have problems such as low mechanical strength (easily ruptured during dressing processing) and poor responsiveness (unable to accurately release active ingredients in specific wound conditions).

[0019] Based on this, one embodiment of the present invention provides a microcapsule wound dressing containing cannabidiol, comprising polyurethane foam and functional microcapsules dispersed in the polyurethane foam; the functional microcapsules comprise a urea-formaldehyde resin microcapsule matrix and cannabidiol located inside the microcapsule matrix; the functional microcapsules account for 5%-15% of the mass of the polyurethane foam. In this embodiment, the urea-formaldehyde resin microcapsules are combined with the polyurethane foam, and through the synergistic design of microcapsules responding to release active ingredients and foam matrix managing the wound environment, the technical problems of poor stability of cannabidiol, low controllability of release, and difficulty in managing exudate from chronic wounds are solved. The resulting wound dressing can combine precise response release of microcapsules, efficient exudate management, and stable performance of active ingredients, solving the technical problems of long healing cycles and high nursing difficulty of chronic wounds.

[0020] In some embodiments, the raw materials for the urea-formaldehyde resin microcapsule matrix include urea and formaldehyde, with a molar ratio of urea to formaldehyde of 1:1.5-2.0. By controlling the molar ratio of urea to formaldehyde, the degree of crosslinking of the urea-formaldehyde resin matrix can be adjusted. A molar ratio of 1:1.5-2.0 provides a moderate degree of crosslinking, ensuring both mechanical strength and responsive rupture capability. This avoids the problems of premature rupture of microcapsules during processing due to excessively low crosslinking, leading to CBD loss, or excessively high crosslinking, resulting in ineffective CBD release. These embodiments ensure that the functional microcapsules do not rupture during polyurethane foam processing, maintaining CBD stability, and precisely releasing CBD upon contact with wound exudate. This creates a release-management synergy with the exudate absorption function of the polyurethane foam, improving wound healing efficiency.

[0021] In some embodiments, the raw materials for the urea-formaldehyde resin microcapsule matrix also include a modifier, namely polyvinyl alcohol (PVA), with the amount of PVA added being 5%-10% of the mass of urea. PVA improves the flexibility of the urea-formaldehyde resin, preventing the matrix from cracking during foam mixing and compounding due to excessive brittleness. It also enhances the interfacial bonding between the microcapsules and the polyurethane foam, reducing microcapsule detachment. The modified microcapsules bond more tightly to the polyurethane foam matrix, ensuring uniform dispersion of the microcapsules within the foam and preventing excessively high (wound irritation) or excessively low (poor healing) local CBD concentrations, thereby achieving uniform release and action of CBD.

[0022] In some embodiments, cannabidiol (CBD) constitutes 20%-40% of the mass of the functional microcapsules. This 20%-40% CBD mass fraction balances the single-release dose and release duration. Below 20% CBD results in insufficient CBD concentration and poor anti-inflammatory effects, while above 40% leads to an excessively high proportion of microcapsule core material, reducing the matrix's mechanical strength and affecting dressing processing. Simultaneously, this mass percentage range keeps the overall CBD content in the wound dressing at a low level, ensuring good safety.

[0023] In some embodiments, the urea-formaldehyde resin microcapsule matrix has a wall thickness of 0.5-2 μm, and the functional microcapsules have a particle size of 5-20 μm. A wall thickness of 0.5-2 μm achieves a balance between stability and responsiveness. Wall thicknesses below 0.5 μm are prone to rupture, leading to premature CBD loss; thicknesses above 2 μm result in poor responsiveness and inability to release CBD in a timely manner. Furthermore, the wall thickness design ensures the microcapsules are stable during polyurethane foam storage and rupture rapidly upon contact with wound exudate, enabling on-demand release of CBD. The particle size of the functional microcapsules facilitates uniform dispersion within the polyurethane foam, reducing the risk of aggregation and further improving the efficacy of the wound dressing.

[0024] In some embodiments, the raw materials for the polyurethane foam include polyether polyol and isocyanate, with an NCO / OH molar ratio of isocyanate to polyether polyol of 1.05-1.15. An NCO / OH molar ratio of 1.05-1.15 can control the crosslinking density of the polyurethane foam, ensuring high porosity (e.g., 80%-90%) and excellent elastic resilience, preventing wound compression due to foam collapse. Furthermore, the high-porosity foam not only efficiently absorbs exudate but also provides a uniform dispersion space for microcapsules, preventing microcapsule aggregation and synergistically enhancing the overall performance of the dressing in conjunction with the dispersion of functional microcapsules.

[0025] In some embodiments, the exudate absorption capacity of the polyurethane foam is 10-15 times its own weight. This 10-15 times absorption capacity can meet the care needs of chronic wounds (e.g., 5-10 mL of exudate per day) for 3-5 days, reducing the frequency of dressing changes and lowering the risk of secondary wound damage.

[0026] In some embodiments, the CBD release rate of the functional microcapsules is: ≥60% at 24h and ≥90% at 72h under pH 7.0 conditions. The 60% release at 24h rapidly inhibits inflammation, and the 90% release at 72h continuously promotes repair, matching the process of chronic wound healing and promoting the healing of chronic wounds.

[0027] Another embodiment of the present invention provides a method for preparing the above-mentioned microcapsule wound dressing containing cannabidiol, comprising the following steps: S101: Preparation of cannabidiol emulsion: Mix cannabidiol, emulsifier and deionized water, and stir to form an emulsion.

[0028] S102: In-situ polymerization preparation of functional microcapsules: Urea was added to the emulsion, the pH was adjusted and formaldehyde was added dropwise, the polymerization was carried out under heat, a modifier was added, and the reaction was completed and the microcapsules were separated and dried to obtain functional microcapsules.

[0029] S103: Composite preparation of dressing: Polyether polyol, isocyanate, foaming agent and catalyst are mixed, functional microcapsules are added, and after stirring, foaming and curing are carried out to obtain microcapsule wound dressing.

[0030] In the above preparation method, the process of combining in-situ polymerization and foam impregnation can realize the one-step preparation and uniform compounding of microcapsules, avoiding the microcapsule agglomeration caused by traditional physical mixing; the particle size of the dispersed phase of the emulsion can be controlled during the in-situ polymerization process, for example, the particle size of the functional microcapsules can meet the requirements of 5-20μm.

[0031] In some embodiments, in S101, the emulsifier is Tween 80, and the amount added is 10-30% of the mass of cannabidiol; In some embodiments, in S101, the stirring speed is 3000-5000 r / min and the stirring time is 30-60 min; In some embodiments, in S102, the polymerization temperature is 60-70℃ and the polymerization time is 2-4 hours; in S103, the foaming and curing temperature is 60-80℃ and the curing time is 12-24 hours. A polymerization temperature of 60-70℃ avoids CBD degradation due to high temperatures, and a polymerization time of 2-4 hours ensures sufficient cross-linking of the urea-formaldehyde resin, achieving the required matrix wall thickness. A curing temperature of 60-80℃ promotes complete curing of the polyurethane foam, preventing residual isocyanate from irritating wounds, and a curing time of 12-24 hours ensures the stability of the foam structure.

[0032] In some embodiments, in S102, the pH is adjusted to 3.5-4.5.

[0033] In some embodiments, in S103, the foaming agent is n-pentane, and the amount added is 5-10% of the mass of the polyether polyol.

[0034] In some embodiments, in S103, the catalyst is triethylenediamine, and the amount added is 0.5-1% of the mass of the polyether polyol.

[0035] The following are examples and comparative examples.

[0036] Example 1 The method for preparing the wound dressing in this embodiment is as follows: S101: Preparation of Cannabidiol Emulsion: Mix cannabidiol, emulsifier Tween 80, and deionized water, and stir to form an emulsion. The stirring speed is 4000 r / min, and the stirring time is 40 min. The amount of Tween 80 added is 10% of the mass of cannabidiol.

[0037] S102: In-situ polymerization preparation of functional microcapsules: Urea was added to the emulsion, the pH was adjusted, formaldehyde was added dropwise, polymerization was carried out at a controlled temperature, polyvinyl alcohol (PVA) was added as a modifier, and the mixture was separated and dried after the reaction to obtain functional microcapsules. The pH was adjusted to 4 with hydrochloric acid. The polymerization temperature was 65℃, and the polymerization time was 3 hours. The amount of PVA added was 8% of the mass of urea.

[0038] S103: Composite Preparation of Dressing: Polyether polyol, isocyanate, foaming agent, and catalyst are mixed, functional microcapsules are added, and the mixture is stirred and then foamed and cured to obtain a microcapsule wound dressing. The foaming agent is n-pentane, added at 8% of the mass of the polyether polyol. The catalyst is triethylenediamine, added at 0.5% of the mass of the polyether polyol. The foaming and curing temperature is 70℃, and the curing time is 15h.

[0039] The preparation methods of other embodiments and comparative examples are similar to those of Example 1.

[0040]

[0041] Comparative Example 1 Compared with Example 1, the difference is that the urea-formaldehyde resin microcapsule matrix is ​​replaced with gelatin.

[0042] Comparative Example 2 Compared to Example 1, there are no functional microcapsules, and the wound dressing is polyurethane foam.

[0043] Comparative Example 3 The difference compared to Example 1 is that: there is no urea-formaldehyde resin microcapsule matrix, and cannabidiol is directly dispersed in polyurethane foam.

[0044] Comparative Example 4 The difference compared to Example 1 is that the functional microcapsules account for 20% of the mass of the polyurethane foam.

[0045] Test case (1) Stability of wound dressing The samples were stored at 40°C and 75% RH for 30 days, and the CBD retention rate was detected (high performance liquid chromatography, HPLC). The CBD retention rate was used to represent the stability of the wound dressing.

[0046] Detection procedure: Take 0.5g of the sample before and after storage, add 5mL of methanol, and extract ultrasonically for 30min. After filtration, take the supernatant and determine the CBD peak area using HPLC (column: C18 column, mobile phase: methanol:water = 85:15, flow rate: 1mL / min, detection wavelength: 220nm). Calculate the retention rate according to the formula: CBD retention rate (%) = (CBD peak area after storage / CBD peak area before storage) × 100%.

[0047] (2) CBD release rate Take 0.5 g of sample, wrap it in a dialysis bag, and place it in 50 mL of pH 7.0 PBS buffer. Incubate at 37°C with constant shaking (100 rpm). Take 5 mL samples at 24 h and 72 h (with an equal amount of fresh PBS added simultaneously). Determine the CBD concentration using HPLC and calculate the release rate according to the formula: CBD release rate (%) = (cumulative CBD release mass / total CBD mass in sample) × 100%.

[0048] (3) Exudate absorption The sample was first dried at 105℃ to constant weight (mass m0), cooled to room temperature, and then immersed in simulated exudate. After 24 hours, it was removed, the surface liquid was blotted dry with filter paper, and the sample was weighed (mass m1). The absorption amount was calculated according to the formula: Exudate absorption (times) = (m1-m0) / m0.

[0049] (4) Wound healing effect A diabetic rat foot ulcer model (induced by streptozotocin) was used. Ten rats were in each group. The sample was applied to the ulcer wound (1cm×1cm area). The dressing was changed once a week. The wound healing rate was measured after 14 days. ImageJ software was used to analyze wound photographs, calculate the wound area (S), and calculate the healing rate using the formula: Wound healing rate (%) = (initial wound area - wound area at the time of measurement) / initial wound area × 100%.

[0050] (5) Skin irritation The sample extract (0.9% NaCl solution, 1g sample / 10mL extract, 37℃ for 24h) was applied to the hairless skin on the back of the rabbit (area 2cm×2cm). The application was repeated for 7 days. The redness and erythema of the skin were observed and graded as no irritation (level 0), slight irritation (level 1), moderate irritation (level 2), and severe irritation (level 3).

[0051] The test results are shown in the table below.

[0052]

[0053] As can be seen from the table above, (1) The CBD retention rate of Examples 1-5 was ≥94%, which was significantly higher than that of Comparative Example 1 (gelatin matrix) and Comparative Example 3 (CBD was not encapsulated), proving that the urea-formaldehyde resin matrix can effectively isolate oxygen and light, and improve the stability of CBD.

[0054] (2) The CBD release of Examples 1-5 was ≥60% at 24h and ≥90% at 72h, which can rapidly inhibit inflammation (early release) and continuously promote repair (late release). In contrast, Comparative Examples 1 and 3 had burst release problems and irritated the skin, proving that the pH responsiveness of the urea-formaldehyde resin matrix can achieve precise release and reduce skin irritation.

[0055] (3) The exudate absorption of Examples 1-5 was ≥14 times, which was close to that of Comparative Example 2 (polyurethane foam only), proving that the addition of microcapsules did not affect the pore structure of polyurethane foam. However, in Comparative Example 4, the absorption decreased due to the blockage of pores by excessive microcapsule content, resulting in a reduced wound healing rate and some skin irritation.

[0056] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

[0057] For those skilled in the art, based on the ideas of this invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of this invention.

Claims

1. A microcapsule wound dressing containing cannabidiol, characterized in that: The invention comprises polyurethane foam and functional microcapsules dispersed in the polyurethane foam; the functional microcapsules comprise a urea-formaldehyde resin microcapsule matrix and cannabidiol located within the microcapsule matrix; the functional microcapsules constitute 5%-15% of the mass of the polyurethane foam.

2. The microcapsule wound dressing containing cannabidiol as described in claim 1, characterized in that: The raw materials for the urea-formaldehyde resin microcapsule matrix include urea and formaldehyde, and the molar ratio of urea to formaldehyde is 1:1.5-2.

0.

3. The microcapsule wound dressing containing cannabidiol as described in claim 2, characterized in that: The raw materials for the urea-formaldehyde resin microcapsule matrix also include a modifier, which is polyvinyl alcohol, and the amount of polyvinyl alcohol added is 5%-10% of the mass of the urea.

4. The microcapsule wound dressing containing cannabidiol as described in claim 1, characterized in that: The cannabidiol accounts for 20%-40% of the mass of the functional microcapsule.

5. The microcapsule wound dressing containing cannabidiol as described in claim 1, characterized in that: The wall thickness of the urea-formaldehyde resin microcapsule matrix is ​​0.5-2 μm, and the particle size of the functional microcapsules is 5-20 μm.

6. The microcapsule wound dressing containing cannabidiol as described in claim 1, characterized in that: The raw materials for the polyurethane foam include polyether polyol and isocyanate, wherein the NCO / OH molar ratio of the isocyanate to the polyether polyol is 1.05-1.

15.

7. The microcapsule wound dressing containing cannabidiol as described in any one of claims 1-6, characterized in that: The polyurethane foam absorbs 10-15 times its own mass in exudate.

8. The microcapsule wound dressing containing cannabidiol as described in any one of claims 1-6, characterized in that: The CBD release rate of the functional microcapsules is ≥60% after 24 hours and ≥90% after 72 hours at pH 7.

0.

9. The method for preparing the microcapsule wound dressing containing cannabidiol as described in any one of claims 1-8, characterized in that: Includes the following steps: S101: Preparation of cannabidiol emulsion: Mix cannabidiol, emulsifier and deionized water, and stir to form an emulsion; S102: In-situ polymerization preparation of functional microcapsules: Urea was added to the emulsion, the pH was adjusted and formaldehyde was added dropwise, the polymerization was carried out under heat, a modifier was added, and the reaction was completed and the microcapsules were separated and dried to obtain functional microcapsules. S103: Composite preparation of dressing: Polyether polyol, isocyanate, foaming agent and catalyst are mixed, functional microcapsules are added, and after stirring, foaming and curing are carried out to obtain microcapsule wound dressing.

10. The preparation method according to claim 9, characterized in that: In S101, the emulsifier is Tween 80, and the amount added is 10-30% of the mass of cannabidiol. In S101, the stirring speed is 3000-5000 r / min, and the stirring time is 30-60 min; In S102, the polymerization temperature is 60-70℃ and the polymerization time is 2-4h; In S103, the foaming and curing temperature is 60-80℃, and the curing time is 12-24h; In S103, the foaming agent is n-pentane, and the amount added is 5-10% of the mass of the polyether polyol; In S103, the catalyst is triethylenediamine, and the amount added is 0.5-1% of the mass of the polyether polyol.

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