Scar repair patch with immune microenvironment regulation function and application thereof

Abstract

The invention belongs to the technical field of medical supplies, and discloses a scar repair patch with an immune microenvironment adjusting function and application thereof.The scar repair patch comprises a backing layer, a silica gel layer and a protective film layer, the silica gel layer is connected with the backing layer, the backing layer is connected with elastic cloth, and the elastic cloth is connected with a pasting layer; the silica gel layer is prepared from a first silica gel component, a second silica gel component and an immune regulation component, and the immune regulation component is prepared from the following raw materials in parts by mass: 2 to 8 parts of arginine hydrochloride, 0 to 10 parts of chondroitin sulfate, 20 to 35 parts of polyethylene glycol 400, 20 to 35 parts of polydimethylsiloxane, 20 to 35 parts of glycerol, 3 to 10 parts of cetyl PEG / PPG-10 / 1 polydimethylsiloxane and 4 to 10 parts of purified water; meanwhile, the preparation method is optimized, according to the technical scheme, immune cell phenotypes can be actively regulated and controlled, repairing and healing of skin wounds are synergistically promoted, closing of chronic wounds is accelerated, skin regeneration of acute wounds is promoted, scar growth is inhibited, the curative effect of the scar patch is improved, and long-term use of the scar patch is facilitated.

Description

Technical Field

[0001] The present invention relates to the technical field of medical supplies, and in particular to a scar repair patch with immune microenvironment regulation function and its application. Background Art

[0002] Scars, as an inevitable product of the body's wound repair from burns, scalds or surgical operations, etc., are usually irregular, red-colored and hard benign masses, which can cause reactions such as itching and pain and other functional disorders. At the same time, the poor visual appearance also brings great psychological pressure to patients. At present, silicone gel scar patches are recommended by the International Burn Society for the treatment of hypertrophic scars, with significant curative effects and almost no side effects. Silicone gel scar patches mainly act by covering and sealing, and compressing the scar tissue; they play a role in restricting the evaporation of moisture on the scar surface, inhibiting the regeneration of capillaries, maintaining a moist environment, and promoting the hydration of the stratum corneum on the scar surface, thereby softening the scar and lightening the pigmentation.

[0003] Skin wound healing is a complex physiological process, involving four stages: hemostasis, inflammation, proliferation and remodeling. The regulation of the immune microenvironment plays a key role in the wound healing process. However, immune regulation dysfunction may lead to impaired wound healing, forming chronic wounds or scars. Although there are various scar patch products on the market at present, most of them can only provide a physical barrier or simple drug release, lacking precise regulation of the immune microenvironment.

[0004] Traditional scar patches mainly inhibit scar hyperplasia through physical compression or silicone sealing, but their action mechanism is single, and the effect on complex scars (such as hypertrophic scars and keloids) is limited; recent studies have shown that scar formation is closely related to the imbalance of the immune microenvironment during the wound healing period: over-activation of pro-inflammatory M1 macrophages, continuous activation of the TGF-β1 signaling pathway, abnormal deposition of extracellular matrix (ECM), etc. The existing technologies lack a solution for inhibiting scars by actively regulating the phenotypes of immune cells (such as inducing the polarization of M2 macrophages) and the balance of inflammatory factors.

[0005] Based on this, the present invention aims to provide a scar repair patch with immune microenvironment regulation function and its preparation method; it can actively regulate the phenotypes of immune cells (such as inducing the polarization of M2 macrophages and inflammatory factors), accelerate the closure of chronic wounds and promote the skin regeneration of acute wounds, and increase the deep repair of scars, which is of great significance to the medical technology industry. Summary of the Invention

[0006] The present invention aims to provide a scar repair patch with immune microenvironment regulation function and its application to solve the problems raised in the above background art.

[0007] To achieve the above object, the present invention provides the following technical solutions: A scar repair patch with the function of regulating immune microenvironment, comprising a backing layer, a silicone gel layer and a protective film layer. The silicone gel layer is connected to the backing layer. The backing layer is connected with an elastic cloth, and the elastic cloth is connected with an adhesive layer; The silicone gel layer is composed of a first silicone gel component, a second silicone gel component and an immune regulation component. The immune regulation component includes the following raw materials by mass ratio: 2-8 parts of arginine hydrochloride, 0-10 parts of chondroitin sulfate, 20-35 parts of polyethylene glycol 400, 20-35 parts of polydimethylsiloxane, 20-35 parts of glycerol, 3-10 parts of cetyl PEG / PPG-10 / 1 polydimethylsiloxane, and 4-10 parts of purified water.

[0008] Preferably, the mass ratio of the immune regulation component to the first silicone gel component and the second silicone gel component is 1:9-11:9-11.

[0009] Preferably, the backing layer is one of a silicone rubber film, a polyurethane film or a non-woven fabric.

[0010] Preferably, the thickness of the silicone gel layer is 0.2-2 mm.

[0011] Preferably, the protective film layer is a polyethylene film or a polypropylene film.

[0012] Preferably, the thickness of the backing layer is 0.01-0.2 mm.

[0013] Preferably, the thickness of the protective film layer is 0.01-0.15 mm.

[0014] A preparation method of a scar repair patch with the function of regulating immune microenvironment, characterized by comprising the following steps: S1. Prepare the immune regulation component; S11. Select corresponding raw materials according to the set mass components, add polyethylene glycol 400 and glycerol to water and mix, then add arginine hydrochloride to water and stir to dissolve to obtain an aqueous phase; S12. Mix cetyl PEG / PPG-10 / 1 polydimethylsiloxane and polydimethylsiloxane to obtain an oil phase, and heat the oil phase for standby; S13. Add the aqueous phase to the oil phase and stir at a stirring speed of 13000-15000 rpm for 10-20 min to obtain the immune regulation component; S2. Prepare the silicone gel solution; S21. Add the second silicone gel component to the immune regulation component and stir to mix to obtain a premixed composition; S22. Add the first silicone gel component to the premixed composition and stir to mix to obtain the silicone gel solution; S3. Coat the silicone gel solution on the backing layer, then cure it at room temperature for 30 - 60 min, and then continue to fix it at a temperature of 60 - 80 °C for 30 - 60 min to obtain a silicone gel repair patch; S4. Cover the silicone gel repair patch with a protective film layer to obtain a scar repair patch.

[0015] Preferably, in S12, heat the oil phase to 60 - 65 °C for standby, and in S13, add the water phase to the oil phase and stir at an ambient temperature of 60 - 65 °C.

[0016] Preferably, the scar repair patch is used for repairing scars.

[0017] Beneficial effects of this technical solution compared with the prior art: (1) The silicone gel layer in the scar repair patch provided by the present invention contains immune regulation components, which can regulate the immune microenvironment; through the mutual cooperation and synergistic compounding effect between the silicone gel solution and the immune regulation components, it can actively regulate the phenotype of immune cells, synergistically promote the repair and healing of skin wounds, accelerate the closure of chronic wounds and promote the regeneration of acute wound skin, inhibit scar growth, improve the curative effect of the scar patch, and is beneficial to the long-term use of the scar patch.

[0018] (2) The present invention optimizes the process for preparing the silicone gel layer. By using a step-by-step mixing method to complete the preparation of the silicone gel layer, hydrophilic components such as thermosensitive gels and natural active scar-removing components can be evenly distributed in the silicone gel composite adhesive layer at the same time. As the sweating or body surface temperature rises, it can contact and absorb sweat faster, and fully exert the antibacterial, anti-inflammatory, sweat-inhibiting and itching-relieving effects of the natural active scar-removing components, improving the use effect of the scar repair patch; and the preparation method is simple, convenient for large-scale production and use, with low preparation cost and convenient for industrial application. Brief Description of the Drawings

[0019] Figure 1 It is a flow chart of the preparation method provided by the present invention; Figure 2 It is a result diagram of the test experiment provided by the present invention; Figure 3 It is a structural diagram of the scar repair patch provided by the present invention; Reference numerals: backing layer 1, elastic cloth 2, pasting layer 3. Detailed Embodiments

[0020] The present invention will be further described in detail below with reference to the drawings and embodiments: A scar repair patch with an immune microenvironment regulation function includes a backing layer 1, a silicone gel layer and a protective film layer. The silicone gel layer is connected to the backing layer 1. The backing layer 1 is connected with an elastic cloth 2, and the elastic cloth 2 is connected with a pasting layer 3; The backing layer 1 is one of a silicone rubber film, a polyurethane film or a non-woven fabric; the protective film layer is a polyethylene film or a polypropylene film; the thickness of the silicone gel layer is 0.2 - 2 mm. The thickness of the backing layer 1 is 0.01 - 0.2 mm. The thickness of the protective film layer is 0.01 - 0.15 mm.

[0021] The silicone gel layer is composed of a first silicone gel component, a second silicone gel component and an immune regulation component. The mass ratio of the immune regulation component to the first silicone gel component and the second silicone gel component is 1:9 - 11:9 - 11. The immune regulation component includes the following raw materials by mass ratio, 2 - 8 parts of arginine hydrochloride, 0 - 10 parts of chondroitin sulfate, 20 - 35 parts of polyethylene glycol 400, 20 - 35 parts of polydimethylsiloxane, 20 - 35 parts of glycerol, 3 - 10 parts of cetyl PEG / PPG - 10 / 1 polydimethylsiloxane, and 4 - 10 parts of purified water. The above-mentioned arginine hydrochloride can also be selected as arginine during actual preparation; A preparation method of a scar repair patch with immune microenvironment regulation function, = includes the following steps, S1. Prepare the immune regulation component; S11. Select corresponding raw materials according to the set mass components, add polyethylene glycol 400 and glycerol to water and mix, then add arginine hydrochloride to water and stir to dissolve to obtain an aqueous phase; S12. Mix cetyl PEG / PPG - 10 / 1 polydimethylsiloxane and polydimethylsiloxane to obtain an oil phase, and heat the oil phase to 60 - 65 °C for standby; S13. Add the aqueous phase to the oil phase at a temperature of 60 - 65 °C and stir at a stirring speed of 13000 - 15000 rpm for 10 - 20 min to obtain the immune regulation component; S2. Prepare the silicone gel liquid; S21. Add the second silicone gel component to the immune regulation component and stir to mix to obtain a premixed composition; S22. Add the first silicone gel component to the premixed composition and stir to mix to obtain the silicone gel liquid; S3. Coat the silicone gel liquid on the backing layer 1, then cure it at room temperature for 30 - 60 min, and then continue to fix it at a temperature of 60 - 80 °C for 30 - 60 min to obtain a silicone gel repair patch; S4. Cover the protective film layer on the silicone gel repair patch to obtain the scar repair patch.

[0022] Example 1, A scar repair patch with immune microenvironment regulation function, including a backing layer 1, a silicone gel layer and a protective film layer. The silicone gel layer is connected to the backing layer 1. The backing layer 1 is connected with an elastic cloth 2. The elastic cloth 2 is connected with a pasting layer 3. The pasting layer 3 is connected with a release layer, which is convenient for subsequent pasting of the scar repair patch; The backing layer 1 is made of non-woven fabric; the protective film layer is a polyethylene film; the thickness of the backing layer 1 is 0.1 mm; the thickness of the protective film layer is 0.08 mm.

[0023] The silicone gel layer is composed of a first silicone gel component, a second silicone gel component, and an immune regulation component. The raw materials of the immune regulation component are selected by mass as follows: 4 g of arginine hydrochloride, 3 g of chondroitin sulfate, 28 g of polyethylene glycol 400, 26 g of polydimethylsiloxane, 25 g of glycerol, 6 g of cetyl PEG / PPG-10 / 1 polydimethylsiloxane, and 8 g of purified water.

[0024] A preparation method of a scar repair patch with an immune microenvironment regulation function includes the following steps. S1. Prepare the immune regulation component; all the raw materials used below are the raw materials selected by the above mass. S11. Add polyethylene glycol 400 and glycerol to water and mix, then add arginine hydrochloride to the water and stir to dissolve to obtain an aqueous phase. S12. Mix cetyl PEG / PPG-10 / 1 polydimethylsiloxane and polydimethylsiloxane to obtain an oil phase, and heat the oil phase to 63 °C for standby. S13. Add the aqueous phase to the oil phase at a temperature of 63 °C and stir at a stirring speed of 14000 rpm for 15 min to obtain the immune regulation component. S2. Prepare the silicone gel liquid. The mass ratio of the immune regulation component, the first silicone gel component, and the second silicone gel component is 1:9.5:1.05. S21. Add the second silicone gel component to the immune regulation component and stir to mix to obtain a premixed composition. S22. Add the first silicone gel component to the premixed composition and stir to mix to obtain the silicone gel liquid. S3. Coat the silicone gel liquid on the backing layer 1, then cure it at room temperature for 45 min, and then continue to fix it at a temperature of 70 °C for 45 min to obtain a silicone gel repair patch. S4. Cover the protective film layer on the silicone gel repair patch to obtain a scar repair patch; the thickness of the silicone gel layer of the obtained scar repair patch is 1 mm.

[0025] Example 2 A scar repair patch with an immune microenvironment regulation function includes a backing layer 1, a silicone gel layer, and a protective film layer. The silicone gel layer is connected to the backing layer 1, the backing layer 1 is connected to an elastic cloth 2, the elastic cloth 2 is connected to a pasting layer 3, and the pasting layer 3 is connected to a release layer, which is convenient for subsequent pasting of the scar repair patch. The backing layer 1 is made of non-woven fabric; the protective film layer is a polyethylene film; the thickness of the silicone gel layer is 1 mm; the thickness of the backing layer 1 is 0.1 mm; the thickness of the protective film layer is 0.08 mm.

[0026] The silicone gel layer is composed of a first silicone gel component, a second silicone gel component and an immune regulation component. The raw materials of the immune regulation component are selected by the following mass: 5 g of arginine hydrochloride, 28 g of polyethylene glycol 400, 26 g of polydimethylsiloxane, 26 g of glycerol, 6 g of cetyl PEG / PPG-10 / 1 polydimethylsiloxane, and 9 g of purified water.

[0027] A preparation method of a scar repair patch with immune microenvironment regulation function includes the following steps: S1. Prepare the immune regulation component; all the raw materials used below are the raw materials selected by the above mass. S11. Add polyethylene glycol 400 and glycerol to water and mix, then add arginine hydrochloride to water and stir to dissolve to obtain an aqueous phase. S12. Mix cetyl PEG / PPG-10 / 1 polydimethylsiloxane and polydimethylsiloxane to obtain an oil phase, and heat the oil phase to 63 °C for standby. S13. Add the aqueous phase to the oil phase at a temperature of 63 °C and stir at a stirring speed of 14000 rpm for 15 min to obtain the immune regulation component. S2. Prepare the silicone gel solution. The mass ratio of the immune regulation component, the first silicone gel component and the second silicone gel component is 1:9.5:1.05. S21. Add the second silicone gel component to the immune regulation component and stir to mix to obtain a premixed composition. S22. Add the first silicone gel component to the premixed composition and stir to mix to obtain the silicone gel solution. S3. Coat the silicone gel solution on the backing layer 1, then cure it at room temperature for 45 min, and then continue to fix it at a temperature of 70 °C for 45 min to obtain the silicone gel repair patch. S4. Cover the protective film layer on the silicone gel repair patch to obtain the scar repair patch.

[0028] Conduct a test on the water permeability of the product. The test steps include: S1. Prepare a thermostatic and humidistatic chamber, set the parameters of the thermostatic and humidistatic chamber to a temperature of 37 °C and a humidity of 15%, turn on the thermostatic and humidistatic chamber in advance, and conduct the test after the equipment runs stably. S2. Cut the sample of the test material into a square with a side length of 4.5 cm to obtain the test sample; adjust the state and conduct the test of the test sample under the conditions of (21±2)°C and a relative humidity of (60±15)%; the state adjustment time of the test sample should be not less than 16 h.

[0029] S3. Add sufficient deionized water to the test container at room temperature (minimum 20°C) so that the air gap between the liquid level and the placed test sample is (5±1) mm; S4. Precisely cover the cut test sample on the flange of the test container, clamp the test sample without deforming it, and form a water seal between the clamping plate and the cover plate; repeat this step 4 times to prepare a total of 5 samples, S5. Weigh and record the mass of the test container, the test sample, and the liquid, and record this mass as W1, with the weighing accurate to 0.0001 g S6. Place the test container in a stable thermostatic and humidistatic chamber with the test sample facing upward.

[0030] S7. After 24 h, take out each container from the thermostatic and humidistatic chamber, record the test time and mark it as T, with the time accurate to 5 min.

[0031] S8. Without cooling, immediately reweigh the test container, the test sample, and the liquid, and record this mass as W2, with the weighing accurate to 0.0001 g.

[0032] S9. Calculate the water vapor transmission rate, and the water vapor transmission rate is calculated according to the following formula: X = (W1 - W2)×1000×24 / T In the formula: X—the water vapor transmission rate, with the unit of grams per square meter per 24 hours (g·m -2 ·24h -1 ); W1 is the mass of the test container, the test sample, and the liquid recorded in step S5 above, with the unit of grams (g); W2 is the mass of the test container, the test sample, and the liquid recorded in step S8 above, with the unit of grams (g); T is the test period time recorded in step S7 above, with the unit of hours (h).

[0033] Conduct experiments on the samples prepared in Example 1 and Example 2 and the prior art purchased on the market according to the above steps, and the results are as follows in the table: The technical solution proposed by the present invention has a higher water vapor transmission rate and better use effects.

[0034] Test for the wound healing effect: Thirty-six adult SD rats with similar body sizes were divided into 3 groups; the mass of SD rats was controlled at 200–230 g; the SD rats were anesthetized with a mixture of chloral hydrate and sodium pentobarbital and fixed on the operating board; a wound with a diameter of 1 cm was cut at the same position on the back of each SD rat; they were treated with normal saline, commercially available scar stickers, and the self-made scar stickers prepared in Example 1 respectively; each group had three parallel samples; the target tissues taken from the rats on the 7th day and the 14th day were used for histomorphological examination; The target tissues of SD rats were fixed with 4% paraformaldehyde for 24 h, dehydrated with 30% sucrose solution for 48 h, and then the samples were embedded in optimal cutting temperature compound to cut into 5-μm-thick sections; after rinsing once with phosphate buffered saline (PBS), the slides were stained with hematoxylin and eosin; For immunofluorescence analysis, the frozen sections of the wound tissue samples were first washed 3 times with phosphate buffered saline (PBS) (5 minutes each time); Tris-buffered saline (TBS) containing 0.025% (v / v) Triton X-100, 0.3 M (w / v) glycine, and 3% (w / v) bovine serum albumin (BSA) was used to block non-specific protein-protein interactions at room temperature for 1 hour; then the frozen sections were incubated overnight at 4°C with antibody CD31 (Abcam, 1 μg / mL) containing 0.025% (v / v) Triton X-100 and 3% (w / v) bovine serum albumin (BSA) in Tris-buffered saline (TBS) containing 0.025% (v / v) Triton X-100 and 3% (w / v) bovine serum albumin (BSA).

[0035] Then the frozen sections were incubated with a goat polyclonal secondary antibody of mouse IgG-H&L (Alexa Fluor 47, Abcam) and 4,6-diamidino-2-phenylindole (DAPI) for 1 hour; then the slides were examined using a fluorescence microscope.

[0036] The inspection results are as shown in the accompanying drawings of the specification Figure 2 as follows, wherein A is a diagram of the histomorphological evaluation of the normal saline solution, commercially available scar sticker group, and self-made scar sticker group.

[0037] B is a schematic diagram of immunostaining of neovascularization, CD31 (red), and cell nuclei (blue) (scale bar = 50 μm).

[0038] It can be seen from this that on the 7th day of treatment, obvious defects appeared in the epidermal and dermal structures of the normal saline group; in the commercially available scar patch group and the self-made scar patch group, the reconstruction of functional skin had begun and they were in the stage of epithelial regeneration; on the 14th day of treatment, compared with the normal saline group and the commercially available scar patch group, the reconstructed epithelium of the self-made scar patch group was the thickest and was almost completely epithelialized. This result indicates that the technical solution proposed in this application is significantly superior to the commercially available scar patch in wound healing and scar repair.

[0039] The above are only embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics known in the solution are not described in detail here. It should be noted that for those skilled in the art, without departing from the technical solution of the present invention, several deformations and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the implementation effect of the present invention and the practicability of the patent. The protection scope required by this application should be subject to the content of its claims, and the specific implementation manners described in the specification can be used to interpret the content of the claims.

Claims

1. A scar repair patch with the function of regulating immune microenvironment, characterized in that: It includes a backing layer (1), a silicone gel layer and a protective film layer. The silicone gel layer is connected to the backing layer (1). The backing layer (1) is connected to an elastic cloth (2), and the elastic cloth (2) is connected to an adhesive layer (3). The silicone gel layer is composed of a first silicone gel component, a second silicone gel component and an immune regulation component. The immune regulation component includes the following raw materials by mass ratio: 2-8 parts of arginine hydrochloride, 0-10 parts of chondroitin sulfate, 20-35 parts of polyethylene glycol 400, 20-35 parts of polydimethylsiloxane, 20-35 parts of glycerol, 3-10 parts of cetyl PEG / PPG-10 / 1 polydimethylsiloxane, and 4-10 parts of purified water.

2. The scar repair patch with the function of regulating immune microenvironment according to claim 1, wherein: The mass ratio of the immune regulation component to the first silicone gel component and the second silicone gel component is 1:9 - 11:9 - 11.

3. The scar repair patch with the function of regulating immune microenvironment according to claim 1, wherein: The backing layer (1) is one of a silicone rubber film, a polyurethane film or a non-woven fabric.

4. The scar repair patch with the function of regulating immune microenvironment according to claim 1, characterized in that: The thickness of the silicone gel layer is 0.2 - 2 mm.

5. The scar repair patch with the function of regulating immune microenvironment according to claim 1, characterized in that: The protective film layer is a polyethylene film or a polypropylene film.

6. The scar repair patch with the function of regulating immune microenvironment according to claim 1, wherein: The thickness of the backing layer is 0.01 - 0.2 mm.

7. The scar repair patch with the function of regulating immune microenvironment according to claim 1, characterized in that: The thickness of the protective film layer is 0.01 - 0.15 mm.

8. The preparation method of a scar repair patch with an immune microenvironment regulation function according to any one of claims 1-7, characterized in that: It includes the following steps S1. Prepare the immune regulation component; S11. Select the corresponding raw materials according to the set mass components. Add polyethylene glycol 400 and glycerol to water and mix, then add arginine hydrochloride to the water and stir to dissolve to obtain an aqueous phase; S12. Mix cetyl PEG / PPG-10 / 1 polydimethylsiloxane and polydimethylsiloxane to obtain an oil phase, and heat the oil phase for standby; S13. Add the aqueous phase to the oil phase and stir at a stirring speed of 13000 - 15000 rpm for 10 - 20 min to obtain the immune regulation component; S2. Prepare the silicone gel liquid; S21. Add the second silicone gel component to the immune regulation component and stir to mix to obtain a premixed composition; S22. Add the first silicone gel component to the premixed composition and stir to mix to obtain the silicone gel liquid; S3. Coat the silicone gel liquid on the backing layer, then cure it at room temperature for 30 - 60 min, and then continue to fix it at a temperature of 60 - 80 °C for 30 - 60 min to obtain a silicone gel repair patch; S4. Cover the protective film layer on the silicone gel repair patch to obtain a scar repair patch.

9. The preparation method of a scar repair patch with an immune microenvironment regulation function as described in claim 8, characterized in that: In S12, heat the oil phase to 60 - 65 °C for standby. In S13, add the aqueous phase to the oil phase and stir at an ambient temperature of 60 - 65 °C.

10. The scar repair patch with the function of regulating immune microenvironment according to claim 1, characterized in that, The scar repair patch is used for repairing scars.

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