Preparation method of hydrogel dressing containing traditional Chinese medicine sustained-release particles

Abstract

The invention relates to a preparation method of a hydrogel dressing containing traditional Chinese medicine sustained-release particles, the preparation method comprises preparation of the traditional Chinese medicine sustained-release particles and preparation of the hydrogel dressing, a cross-linking agent TSPBA adopted by the hydrogel dressing contains phenylboronic acid ester bonds, the ester bonds break after meeting ROS, the traditional Chinese medicine sustained-release particles and magnetic particles are released, and then Chinese herbal medicine components are slowly released; a metal organic framework material adopted by the traditional Chinese medicine sustained-release particles has a free radical scavenging function, so that the content of free radicals at a skin repair part can be reduced, and the overgrowth of fibroblasts can be inhibited; the magnetic particles can generate heat under the action of a magnetic field to inhibit the growth of bacteria and accelerate the release of the traditional Chinese medicine components, so that the inflammatory response during skin repair is further slowed down, and the purpose of synergistically inhibiting the growth of skin scars is achieved. The hydrogel prepared by the invention is stable in performance, the preparation method is simple to operate, complex production equipment is not needed, and macro production is easy to carry out.

Description

Technical Field

[0001] The present invention relates to a method for preparing a novel hydrogel, in particular to a method for preparing a hydrogel dressing containing Chinese medicine sustained-release particles, and specifically to a method for preparing a hydrogel dressing that has ROS response and magnetothermal response and is prepared by containing Chinese medicine sustained-release nanoparticles and magnetic nanoparticle locks and can inhibit scar growth. Background Art

[0002] The formation and proliferation of scars after wound healing has always been a difficult problem to solve in burn treatment. Scars are generally related to factors such as the body's inflammatory response, imbalance in collagen synthesis and degradation, abnormal mucopolysaccharide increase, and myofibroblast proliferation. In the normal process of wound repair, fibroblasts at the edge of the wound proliferate, stimulating the migration and further proliferation of keratinocytes. When the skin tissue is deeply traumatized, an inflammatory response will occur on the wound surface. After white blood cells, mast cells, macrophages and other cells infiltrate the injured skin, they release a large amount of growth factors, causing excessive proliferation and hypertrophy of fibroblasts, and secreting a large amount of extracellular matrix. The typical component of granulation tissue, type III collagen, is replaced by type I collagen, the main component of normal dermis, forming an irregular collagen arrangement, and eventually forming a hypertrophic scar.

[0003] Studies have shown that the formation of hypertrophic scars and keloids is mainly caused by excessive growth of fibroblasts and a large amount of collagen deposition, and excessive generation and accumulation of oxygen free radicals in the local area is also one of the important reasons. Oxygen free radicals can damage the DNA of fibroblasts, cause mutations in certain genes, and increase the proliferation and division of fibroblasts; the oxygen free radicals released in this process, in turn, promote their excessive growth. Therefore, it is urgent to remove free radicals to inhibit scar growth. Summary of the invention

[0004] In response to existing needs, the purpose of the present invention is to provide a method for preparing a hydrogel dressing containing Chinese medicine sustained-release particles, a hydrogel with definite therapeutic effect, Chinese medicine sustained-release ability, magnetothermal response, and the ability to inhibit scar tissue formation, and a preparation method thereof.

[0005] The object of the present invention is achieved by the following scheme: A method for preparing a hydrogel dressing containing Chinese medicine sustained-release particles comprises the following steps: (1) Preparation of sustained-release Chinese medicine granules: After nano-crushing 10 g of Chinese medicine, add 100 mL of ultrapure water to fully soak it, then boil it over high heat, simmer it over low heat for 30 min, discard the precipitate, and continue to heat and concentrate the liquid to 10 mL; fully mix 1-10 g of metal-organic framework material with 10 mL of Chinese medicine extract at room temperature, stir at room temperature for 12-24 h, and collect nanoparticles rich in Chinese medicine by centrifugation; (2) Preparation of hydrogel dressing: Mix 1-10% Chinese medicine sustained-release granules, 1-10% magnetic particles, 0.1%-5% active oxygen crosslinking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diamine (TSPBA), and 2-10% polyvinyl alcohol (PVA), stir thoroughly, and let stand to obtain a hydrogel dressing.

[0006] The metal organic framework structure of the present invention has the effect of scavenging free radicals and can be any one of a cerium-based metal organic framework material, a manganese-based metal organic framework material, and the like.

[0007] The Chinese medicine extract of the present invention is any one or more of Centella asiatica, Lithospermum officinale, Salvia miltiorrhiza, Phellodendron amurense, Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, Cortex fraxini and the like.

[0008] The magnetic particles of the present invention are iron-based nanoparticles with a size less than 20 nm.

[0009] Specifically, it relates to a method for preparing a hydrogel dressing that has ROS response and magnetothermal response, contains Chinese medicine sustained-release nanoparticles and magnetic nanoparticle locks and can inhibit scar growth.

[0010] The advantages of the present invention are: (1) The cross-linking agent TSPBA used in the hydrogel dressing contains a phenyl borate ester bond. When it encounters ROS, the ester bond breaks, releasing the Chinese medicine sustained-release particles and magnetic particles, and then slowly releasing the Chinese herbal medicine components; the metal organic framework material used in the Chinese medicine sustained-release particles has the function of scavenging free radicals, which can reduce the free radical content in the skin repair area and inhibit the excessive growth of fibroblasts; the magnetic particles can generate heat under the action of the magnetic field, inhibit the growth of bacteria, and accelerate the release of Chinese medicine components, further slowing down the inflammatory response during skin repair, thereby achieving the purpose of synergistically inhibiting the growth of skin scars.

[0011] (2) The hydrogel obtained by the present invention has stable performance, the preparation method is simple to operate, does not require complex production equipment, and is easy to carry out large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 Cell viability analysis of the hydrogels prepared in Examples 1-4.

[0013] Depend on Figure 1 It can be seen that compared with the control group, the hydrogel mask prepared in Examples 1-3 can increase the cell viability by more than 80% and has good biocompatibility. DETAILED DESCRIPTION

[0014] The technical scheme of the present invention is further described below through specific examples. The following examples are further explanations of the present invention, but do not limit the scope of the present invention. Example 1

[0015] A hydrogel dressing containing Chinese medicine sustained-release particles is prepared according to the following steps: (1) Preparation of Chinese medicine sustained-release granules: 10g of the Chinese herbal medicine Centella asiatica was nano-crushed, added with 100mL of ultrapure water to fully soak it, and then boiled over high heat. After decocting over low heat for 30 minutes, the precipitate was discarded, and the liquid was heated and concentrated to 10 mL; 2g of the cerium-based metal organic framework material was fully mixed with 10mL of the Chinese herbal medicine extract at room temperature, stirred at room temperature for 12-24h, and the nanoparticles rich in Chinese herbal medicine were collected by centrifugation; (2) Preparation of hydrogel dressing: Mix 5% mass fraction of traditional Chinese medicine sustained-release granules, 5% iron oxide magnetic particles, 0.6% active oxygen cross-linking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diamine (TSPBA) and 6% polyvinyl alcohol (PVA), stir thoroughly, and let stand to obtain a hydrogel dressing.

[0016] The prepared hydrogel mask promotes the proliferation activity of fibroblasts. Figure 1 shown. Example 2

[0017] A hydrogel dressing containing Chinese medicine sustained-release particles is prepared by the following steps, similar to the steps in the embodiment: (1) Preparation of Chinese medicine sustained-release granules: After 10g of lithospermum erythrorhizon nanoparticles were crushed, 100mL of ultrapure water was added to fully soak the mixture, and then the mixture was boiled over high heat. After decocting over low heat for 30min, the precipitate was discarded, and the liquid was heated and concentrated to 10mL. 2g of manganese-based metal organic framework material was fully mixed with 10mL of traditional Chinese medicine extract at room temperature, stirred at room temperature for 12-24h, and the nanoparticles rich in traditional Chinese medicine were collected by centrifugation. (2) Preparation of hydrogel dressing: 4% by mass of Chinese medicine sustained-release granules, 5% of ferroferric oxide magnetic particles, 0.9% of TSPBA and 9% of PVA were mixed, stirred thoroughly and allowed to stand to obtain a hydrogel dressing. Example 3

[0018] A hydrogel dressing containing Chinese medicine sustained-release particles is prepared by the following steps, similar to the steps in the embodiment: (1) Preparation of Chinese medicine sustained-release granules: After 10g of Qinpi nanoparticles were crushed, 100mL of ultrapure water was added to fully soak it, and then it was boiled over high heat. After decocting over low heat for 30min, the precipitate was discarded, and the liquid was heated and concentrated to 10mL; 2g of iron-based metal organic framework material was fully mixed with 10mL of traditional Chinese medicine extract at room temperature, stirred at room temperature for 12-24h, and the nanoparticles rich in traditional Chinese medicine were collected by centrifugation; (2) Preparation of hydrogel dressing: 6% by mass of Chinese medicine sustained-release granules, 6% of ferroferric oxide magnetic particles, 0.6% of TSPBA and 8% of PVA were mixed, stirred thoroughly and allowed to stand to obtain a hydrogel dressing. Example 4

[0019] A hydrogel dressing containing Chinese medicine sustained-release particles is prepared by the following steps, similar to the steps in the embodiment: (1) Preparation of Chinese medicine sustained-release granules: After 10g of Astragalus nanoparticles were crushed, 100mL of ultrapure water was added to fully soak the mixture, and then the mixture was boiled over high heat. After decocting over low heat for 30min, the precipitate was discarded, and the liquid was heated and concentrated to 10mL. 2g of cerium-based metal organic framework materials were fully mixed with 10mL of traditional Chinese medicine extract at room temperature, stirred at room temperature for 12-24h, and the nanoparticles rich in traditional Chinese medicine were collected by centrifugation. (2) Preparation of hydrogel dressing: 8% by mass of Chinese medicine sustained-release granules, 5% of iron oxide magnetic particles, 0.7% of TSPBA, and 7% of PVA are mixed, stirred thoroughly, and allowed to stand to obtain a hydrogel dressing. Performance Testing

[0020] The hydrogel dressing prepared in Example 1-4 was made into a small disc with a diameter of 0.3 mm and spread on the bottom of a 96-well plate. Then, a single well was inoculated with DMEM culture medium (100 μL, 10% calf serum) containing 2000 fibroblasts (L929 cells) and placed in a cell culture incubator (37°C, 5% carbon dioxide (CO 2 ) concentration, 95% relative saturated humidity) for 3 days. Discard the culture medium and thoroughly wash away the residual culture medium with PBS. Add 100µL of serum-free DMEM culture medium containing 10% CCK-8 to each well and culture in an incubator (37°C, 5% carbon dioxide (CO2) concentration, 95% relative saturated humidity) for 2 hours. Then, measure the absorbance of each well at 450nm with an enzyme reader at room temperature.

[0021] Figure 1 The hydrogel mask prepared in Example 1-4 promotes the proliferation activity of fibroblasts. Figure 1 It can be seen that compared with the control group, the hydrogel mask prepared in Examples 1-3 has a cell viability greater than 80% and has good biocompatibility.

Claims

1. A method for preparing a hydrogel dressing containing Chinese medicine sustained-release particles, characterized in that The following steps are involved: (1) Preparation of Chinese medicine sustained-release granules: After 10g of Chinese medicine is nano-crushed, add 100mL of ultrapure water to fully soak it, add it to boil over high heat, simmer it over low heat for 30 minutes, discard the precipitate, and continue to heat the liquid to concentrate it to 10 mL; 1-10g of metal-organic framework material and 10mL of Chinese medicine extract are fully mixed at room temperature, stirred at room temperature for 12-24h, and centrifuged to collect nanoparticles rich in Chinese medicine; (2) Preparation of hydrogel dressing: Mix 1-10% Chinese medicine sustained-release granules, 1-10% magnetic particles, 0.1%-5% active oxygen crosslinking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diamine (TSPBA), and 2-10% polyvinyl alcohol (PVA), stir thoroughly, and let stand to obtain a hydrogel dressing.

2. The method for preparing the hydrogel dressing containing Chinese medicine sustained-release particles according to claim 1, characterized in that The metal organic framework structure has the function of scavenging free radicals and is any one of a cerium-based metal organic framework material and a manganese-based metal organic framework material.

3. The method for preparing the hydrogel dressing containing Chinese medicine sustained-release particles according to claim 1, characterized in that The Chinese herbal medicine extract is any one or more of Centella asiatica, Lithospermum officinale, Salvia miltiorrhiza, Phellodendron amurense, Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, and Fraxinus fraseri.

4. The method for preparing the hydrogel dressing containing Chinese medicine sustained-release particles according to claim 1, characterized in that The magnetic particles are iron-based nanoparticles with a size less than 20 nm.

5. The method for preparing the hydrogel dressing containing Chinese medicine sustained-release particles according to any one of claims 1 to 4, characterized in that: Prepare as follows: (1) Preparation of Chinese medicine sustained-release granules: 10g of the Chinese herbal medicine Centella asiatica was nano-crushed, added with 100mL of ultrapure water to fully soak it, and then boiled over high heat. After decocting over low heat for 30 minutes, the precipitate was discarded, and the liquid was continued to be heated and concentrated to 10 mL; 2g of the cerium-based metal organic framework material was fully mixed with 10 mL of the Chinese herbal medicine extract at room temperature, stirred at room temperature for 12-24 hours, and the nanoparticles rich in Chinese herbal medicine were collected by centrifugation; (2) Preparation of hydrogel dressing: Mix 5% mass fraction of traditional Chinese medicine sustained-release granules, 5% iron oxide magnetic particles, 0.6% active oxygen cross-linking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diamine (TSPBA) and 6% polyvinyl alcohol (PVA), stir thoroughly, and let stand to obtain a hydrogel dressing.

6. The method for preparing the hydrogel dressing containing Chinese medicine sustained-release particles according to any one of claims 1 to 4, characterized in that: Prepare as follows: (1) Preparation of Chinese medicine sustained-release granules: After 10g of lithospermum erythrorhizon nanoparticles were crushed, 100mL of ultrapure water was added to fully soak the mixture, and then the mixture was boiled over high heat. After decocting over low heat for 30min, the precipitate was discarded, and the liquid was heated and concentrated to 10mL. 2g of manganese-based metal organic framework material was fully mixed with 10mL of traditional Chinese medicine extract at room temperature, stirred at room temperature for 12-24h, and the nanoparticles rich in traditional Chinese medicine were collected by centrifugation. (2) Preparation of hydrogel dressing: 4% by mass of Chinese medicine sustained-release granules, 5% of ferroferric oxide magnetic particles, 0.9% of TSPBA and 9% of PVA were mixed, stirred thoroughly and allowed to stand to obtain a hydrogel dressing.

7. The method for preparing the hydrogel dressing containing Chinese medicine sustained-release particles according to any one of claims 1 to 4, characterized in that: Prepare as follows: (1) Preparation of Chinese medicine sustained-release granules: After 10g of Qinpi nanoparticles were crushed, 100mL of ultrapure water was added to fully soak it, and then it was boiled over high heat. After decocting over low heat for 30min, the precipitate was discarded, and the liquid was heated and concentrated to 10mL; 2g of iron-based metal organic framework material was fully mixed with 10mL of traditional Chinese medicine extract at room temperature, stirred at room temperature for 12-24h, and the nanoparticles rich in traditional Chinese medicine were collected by centrifugation; (2) Preparation of hydrogel dressing: 6% by mass of Chinese medicine sustained-release granules, 6% of ferroferric oxide magnetic particles, 0.6% of TSPBA and 8% of PVA were mixed, stirred thoroughly and allowed to stand to obtain a hydrogel dressing.

8. The method for preparing the hydrogel dressing containing Chinese medicine sustained-release particles according to any one of claims 1 to 4, characterized in that: Prepare as follows: (1) Preparation of Chinese medicine sustained-release granules: After 10g of Astragalus nanoparticles were crushed, 100mL of ultrapure water was added to fully soak the mixture, and then the mixture was boiled over high heat. After decocting over low heat for 30min, the precipitate was discarded, and the liquid was heated and concentrated to 10mL. 2g of cerium-based metal organic framework materials were fully mixed with 10mL of traditional Chinese medicine extract at room temperature, stirred at room temperature for 12-24h, and the nanoparticles rich in traditional Chinese medicine were collected by centrifugation. (2) Preparation of hydrogel dressing: 8% by mass of Chinese medicine sustained-release granules, 5% of iron oxide magnetic particles, 0.7% of TSPBA, and 7% of PVA are mixed, stirred thoroughly, and allowed to stand to obtain a hydrogel dressing.

9. A hydrogel dressing containing Chinese medicine sustained-release particles, obtained according to the preparation method according to any one of claims 1 to 8.

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