A gel material with asymmetric adhesion properties and its preparation method and application

Abstract

The present invention belongs to the technical field of medical materials, and discloses a gel material with asymmetric adhesion characteristics, a preparation method and an application thereof. The gel material of the present invention comprises an adhesion layer and a contact layer, wherein the adhesion layer provides viscosity so that the gel material can adhere to skin tissue and can load drugs, thereby facilitating the prevention or repair of skin inflammation caused by radiotherapy; the contact layer is non-adhesive and has good mechanical properties, thereby preventing adhesion to the hands of radiotherapy technicians, and is very convenient for clinical operation.

Description

Technical Field

[0001] The invention relates to the technical field of medical materials, and in particular to a gel material with asymmetric adhesion characteristics and a preparation method and application thereof. Background Art

[0002] Radiotherapy is the most commonly used treatment option for tumors in today's medical field. However, due to the dose-building effect of radiation, when the tumor of some patients invades the skin or is close to the skin, the skin dose will be insufficient, and the cancer cells cannot be completely killed, thus reducing the treatment effect.

[0003] The dose build-up effect refers to the fact that after the radiation photons are irradiated to the human body, the maximum dose point is not on the surface of the human body, but at a certain depth in the body. The area from the body surface to the maximum dose point is called the dose build-up area. In this area, the radiation dose increases with the increase of depth. During radiotherapy, the optimal dose can only be achieved when high-energy rays reach a certain depth in the body. In order to increase the dose in the superficial part, people have come up with a solution: place an object on the surface of the human body. This object has a similar density to the human body, so that the original skin position becomes an area at a certain depth under the skin, and the dose is also increased. This object that adds a certain thickness to the surface of the patient's body to improve the effect of radiotherapy is called a tissue compensator or tissue equivalent (Bolus).

[0004] Traditional commercial tissue compensators have a fixed shape and an immutable thickness. They differ from the shape and curvature of the human body surface and cannot fit closely to the patient's body surface, thus affecting the effect of radiotherapy. 3D printing technology has been increasingly used in the medical field due to its advantages of personalized production, high dimensional accuracy and high conformality. 3D printing technology can be used to produce tissue compensators of specific shapes according to the patient's body surface contour, so that they can fit the skin surface completely, thereby improving the accuracy and stability of the irradiation dose at the lesion. However, whether it is commercial tissue compensators or personalized radiotherapy gel tissue compensators, both sides of the gel have the same adhesion and insufficient biological properties, which is not conducive to actual clinical operation and application. Summary of the invention

[0005] In view of this, the present invention provides a gel material with asymmetric adhesion properties, wherein the gel material comprises an adhesion layer with adhesion characteristics and a contact layer with non-adhesion properties. The gel material is used as a radiotherapy tissue compensator, which greatly facilitates clinical operability.

[0006] The technical solution of the present invention is as follows:

[0007] The present invention provides a gel material with asymmetric adhesion properties, the gel material comprising an adhesion layer and a contact layer;

[0008] The adhesive layer comprises the following raw materials: acrylamide, trehalose, protocatechuic acid, nanoclay, an initiator, a crosslinking agent and an oil-water solvent, wherein the mass ratio of acrylamide, trehalose, protocatechuic acid, nanoclay and the oil-water solvent in the adhesive layer is (20-30): (20-30): (3-6): (0.1-0.15): (90-110), and the molar mass ratio of the crosslinking agent to the acrylamide is 1:400-600;

[0009] The contact layer comprises the following raw materials: acrylamide, trehalose, an initiator, a crosslinking agent and an oil-water solvent. The mass ratio of acrylamide, trehalose and the oil-water solvent in the contact layer is (20-30): (20-40): (90-110), and the molar mass ratio of the crosslinking agent to the acrylamide is 1:50-200.

[0010] In the present invention, as an embodiment, the oil-water solvent is a mixture of glycerol and water, and the mass ratio of glycerol to water is (20-50): (80-50).

[0011] As an embodiment, the crosslinking agent includes polyethylene glycol diacrylate, and the initiator includes LAP initiator.

[0012] As an embodiment, in the adhesion layer and the contact layer, the mass ratio of the initiator to the oil-water solvent of the corresponding layer is independently 0.1:(90-110).

[0013] As an embodiment, the adhesive layer also includes loaded drugs and / or dyes.

[0014] As an embodiment, the loaded drug is an anti-inflammatory agent and / or an antioxidant. The loaded drug is any one or more of resveratrol, curcumin, allicin and gallic acid ester.

[0015] The present invention also provides a method for preparing the above-mentioned gel material, comprising the following steps: mixing the adhesive layer raw materials, photocuring to an incompletely cross-linked state, then mixing the contact layer raw materials and placing them on the adhesive layer, performing secondary photocuring molding to obtain the gel material; or,

[0016] The contact layer raw materials are mixed, and photocured once to an incompletely cross-linked state, and then the adhesive layer raw materials are mixed and placed on the contact layer, and photocured twice to obtain the gel material.

[0017] As an embodiment, the photocuring is performed under a 405nm light source.

[0018] Preferably, the time for the first photocuring is 3-5 seconds, and the time for the second photocuring is more than 10 minutes.

[0019] The present invention also provides the use of the above-mentioned gel material or the method for preparing the gel material in preparing tissue compensation by 3D printing.

[0020] Beneficial effects of the present invention:

[0021] The gel material of the present invention has asymmetric adhesion properties, including an adhesion layer and a contact layer. The adhesion layer provides viscosity so that the gel material can adhere to skin tissue and can load drugs, which is convenient for preventing or repairing skin inflammation caused by radiotherapy; the contact layer is non-adhesive and has good mechanical properties, which can prevent adhesion to the hands of radiotherapy technicians, and is very convenient for clinical operation. The present invention uses trehalose and acrylamide to cross-link under the action of an initiator and a cross-linking agent to form a hydrogel with a double network structure. Trehalose has a water-retaining effect, protocatechuic acid has adhesion and certain anti-inflammatory properties, and nanoclay has a large interface area and a high aspect ratio, which can promote physical or chemical entanglement with polymer chains and improve mechanical properties.

[0022] The key point of preparing the gel material of the present invention is to create a chemical or physical difference between the top and bottom of the gel. The low-viscosity precursor solution composed of the monomer, initiator and cross-linking agent of the contact layer is superimposed on the high-viscosity precursor solution composed of the monomer and additional macromolecules of the adhesion layer. The high viscosity contrast between the two solutions limits the diffusion of the monomers and thus maintains the double-layer structure until the solution is finally solidified into a fixed structure. The constrained molecular exchange occurring at the interface forms an interpenetrating polymer network, which ensures a strong interface bonding strength. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The SEM morphology of the contact layer of the gel material of the present invention is shown in FIG. Figure 2 This is the SEM morphology of the adhesion layer of the gel material of the present invention. It is difficult to find the boundary layer by SEM, which means that the contact layer and the adhesion layer are tightly combined together.

[0024] Figure 3 The figure shows the adhesion of the gel material of the present invention, wherein the contact layer is transparent and the adhesion layer is opaque. It can be seen from the figure that the adhesion layer can adhere to metal, glass, wood and plastic.

[0025] Figure 4 The left side shows the left ear prepared by photocuring printing of the contact layer solution, and the right side shows the right ear prepared by photocuring printing of the adhesion layer solution.

[0026] Figure 5 This is the method for constructing the radiation dermatitis model in the experimental example.

[0027] Figure 6 The HE staining pictures of normal organs of the blank group, the gel group of the present invention and the control group show that the inflammation of normal organs in the control group is more obvious than that in the gel group of the present invention and the blank group.

[0028] Figure 7 The HE staining pictures of the skin of the blank group, the gel group of the present invention and the control group are shown. The inflammation of the skin of the control group is more obvious than that of the gel group of the present invention and the blank group. DETAILED DESCRIPTION

[0029] The invention provides a gel material with asymmetric adhesion properties, comprising an adhesion layer and a contact layer; the adhesion layer comprises the following raw materials: acrylamide, trehalose, protocatechuic acid, nano clay, an initiator, a crosslinking agent and an oil-water solvent, and the contact layer comprises the following raw materials: acrylamide, trehalose, an initiator, a crosslinking agent and an oil-water solvent.

[0030] The present invention comprises a low-viscosity precursor solution composed of acrylamide, trehalose, an initiator and a crosslinking agent in the contact layer, which is superimposed on a high-viscosity precursor solution composed of acrylamide, trehalose monomers and additional macromolecules in the adhesion layer. The high viscosity contrast between the two solutions limits the diffusion of the monomers, thereby maintaining the double-layer structure until the solution is finally solidified into a fixed structure. The constrained molecular exchange occurring at the interface forms an interpenetrating polymer network, ensuring a strong interface bonding strength. Thus, the gel material of the present invention has adhesion properties on one side and can adhere to skin tissue, and does not have adhesion properties on the other side, which is convenient for clinical operation and has asymmetric adhesion characteristics.

[0031] The present invention uses trehalose and acrylamide as monomer raw materials to cross-link under the action of an initiator and a cross-linking agent to form a hydrogel with a double network structure, thereby improving the mechanical properties of the material. At the same time, the C=C double bond in the acrylamide structure ensures the photocurable printability of the material, enabling it to be used for rapid photocurable printing, thereby improving the integrity of the printed structure. Trehalose has a water-retaining effect, and forms a gel through the interaction of hydrogen bonds with acrylamide, thereby improving the comfort of the gel. If the amount of trehalose added is insufficient, the water-retaining performance of the gel decreases. The present invention does not specifically limit the sources of the trehalose and acrylamide, and commercially available products familiar to those skilled in the art may be used.

[0032] The present invention has no particular limitation on the types of initiators and crosslinking agents, and any initiator and crosslinking agent that can initiate molecular crosslinking of acrylamide and trehalose in the prior art can be used.

[0033] The initiator in the present invention is preferably a photoinitiator. The photoinitiator, also known as a photosensitizer or a photocuring agent, is a type of compound that absorbs energy of a certain wavelength in the ultraviolet light region (250-420nm) or the visible light region (400-800nm) to generate free radicals, cations, etc., thereby initiating monomer polymerization and cross-linking and curing. In a specific embodiment of the present invention, the LAP initiator can initiate cross-linking and curing of acrylamide and trehalose under 405nm light irradiation. Preferably, the mass ratio of the LAP initiator to acrylamide is 0.1: (20-30).

[0034] The crosslinking agent is also called a curing agent, a hardener, or a curing agent, and it can transform a linear or slightly branched macromolecule into a three-dimensional network structure. The crosslinking agent in the present invention can optionally include polyethylene glycol diacrylate (PEGDA), or other substances in the prior art that can promote the crosslinking of trehalose and acrylamide to form a double network structure.

[0035] In the gel material of the present invention, acrylamide, trehalose, initiator and crosslinking agent react in an oil-water solvent. Preferably, the oil-water solvent is a mixed binary solvent of glycerol and water. Glycerol has water-retaining properties. The gel material is prone to water loss when placed in the air. Adding glycerol can reduce the material's anti-water loss performance, lock water and keep the gel moist. In the present invention, the mass ratio of glycerol to water is preferably (20-50): (80-50), more preferably (30-45): (70-55).

[0036] In the contact layer of the gel material of the present invention, the mass ratio of acrylamide, trehalose and oil-water solvent is (20-30): (20-40): (90-110), preferably (23-27): (24-35): (95-105); the mass ratio of initiator to oil-water solvent is 0.1: (90-110); the molar mass ratio of crosslinking agent to acrylamide is 1: 50-200, preferably 1: 100-180. Under this ratio, the chemical crosslinking in the gel is more, the gel elastic modulus is larger, and the gel has good mechanical properties.

[0037] In the adhesive layer of the gel material of the present invention, the required raw materials also include protocatechuic acid. In the present invention, the protocatechuic acid can provide skin adhesion, so that the prepared material also has antibacterial properties. If the amount of protocatechuic acid added is too much, the mechanical properties of the gel will decrease and the light curing time will be extended; if the amount added is insufficient, the adhesion of the gel will be insufficient. The present invention does not specifically limit the source of the protocatechuic acid, and commercially available products known to those skilled in the art can be used.

[0038] In the adhesion layer of the gel material of the present invention, the required raw materials also include nano clay. Nano clay has a large interface area and a high aspect ratio, can interact with different polymers, promote physical or chemical entanglement with polymer chains, and improve mechanical properties. Adding nano clay to the adhesion layer of the gel material of the present invention shows better mechanical properties and lasting adhesion properties than the contact layer. The present invention has no particular limitation on the source of the nano clay, and commercial products well known to those skilled in the art can be used.

[0039] In the adhesive layer of the gel material of the present invention, the mass ratio of acrylamide, trehalose, protocatechuic acid, nanoclay, and oil-water solvent is (20-30): (20-30): (3-6): (0.1-0.15): (90-110), preferably (23-27): (23-27): (4-5): (0.11-0.14): (95-105); the mass ratio of initiator to oil-water solvent is 0.1: (90-110); the molar mass ratio of crosslinking agent to acrylamide is 1: 400-600, preferably 1: 450-550. Under the above ratio, the gel can have good tensile properties and softness.

[0040] As an embodiment, a loaded drug may be added to the adhesive layer of the gel material of the present invention to give the gel material special efficacy. If an anti-inflammatory agent and / or an antioxidant is added, the anti-inflammatory agent and / or antioxidant is preferably a natural anti-inflammatory agent and / or antioxidant, such as resveratrol, curcumin, allicin and gallic acid ester. Since the loaded drug is located in the adhesive layer, the adhesive layer can directly act on the human body in contact with the skin to prevent or repair skin inflammation caused by radiotherapy. Preferably, the mass ratio of the loaded drug to the acrylamide is (0.01-0.03): (20-30), and more preferably 0.015-0.025: 21-25.

[0041] The present invention also provides a method for preparing the above-mentioned gel material, that is, first solidify one layer of the gel material, and when solidified to an incompletely cross-linked state, cover another layer of the gel material, and light-cure until it is completely solidified. Specifically, the above-mentioned adhesive layer materials are mixed in proportion, light-cured to an incompletely cross-linked state, and then the contact layer materials are mixed in proportion and placed on the adhesive layer, and then light-cured for a second time to obtain the gel material; or, the contact layer materials are mixed in proportion, light-cured once to an incompletely cross-linked state, and then the adhesive layer materials are mixed in proportion and placed on the contact layer, and then light-cured for a second time to obtain the gel material.

[0042] The present invention does not specifically limit the specific operation mode of photocuring, and the conventional operation mode in the art can be adopted. As an embodiment, the photocuring is carried out under a 405nm light source. Preferably, the time of the first photocuring is 3-5s, so that the gel is in an incompletely cross-linked state; the time of the second photocuring is preferably more than 10min, so that both layers of the gel can be cured and formed to form a gel material. The contact layer and the adhesive layer of the gel material can be tightly connected, the contact layer does not have an adhesive property, and the adhesive layer has good adhesive properties.

[0043] The gel material of the present invention and the above-mentioned preparation method can be used for 3D printing to prepare tissue compensation. As an embodiment, 3D printing to prepare tissue compensation includes the following steps: designing the shape, size and thickness of the tissue compensation according to the requirements, and using a 3D printer to print a casting model of the tissue compensation; mixing the raw materials of the contact layer of the gel material of the present invention in proportion and filling them into the casting model, and photocuring them to an incompletely cross-linked state; then mixing the raw materials of the adhesion layer of the gel material of the present invention in proportion and placing them in the remaining part of the casting model, photocuring and forming, and obtaining a tissue compensation. The tissue compensation prepared by the present invention can also be re-cured, and the re-curing is preferably carried out in a UV lamp oven. In the present invention, the re-curing time is preferably more than 10 minutes.

[0044] As an embodiment, a dye, such as lemon yellow, may be added to the adhesion layer and / or contact layer of the gel material of the present invention to facilitate the preparation of a personalized gel tissue compensation material.

[0045] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is described in detail below in conjunction with embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0046] Example 1

[0047] Single layer contact gel

[0048] 100 g of a glycerol / water mixed system was prepared, and the volume ratio of glycerol to water was 3:7. 20 g of acrylamide, 20 g of trehalose, 0.1 g of LAP initiator and polyethylene glycol diacrylate were added to the system, and the molar mass ratio of the addition amount of polyethylene glycol diacrylate to acrylamide was 1:200, and the gel system 1 was obtained after mixing. The gel system 1 was photocured under a 405 nm light source for 10 min to obtain a gel material, and the gel material was cured again for 10 min to obtain a gel tissue compensation.

[0049] The elastic modulus of the gel is 14.8 kPa, the elongation is 273.8%, the compression modulus is 320 kPa, the strength is 347 kPa, the solution viscosity is 12 cp, and the adhesion strength to pig skin is about 2 kPa.

[0050] Example 2

[0051] Single layer contact gel

[0052] 100 g of a glycerol / water mixed system was prepared, and the volume ratio of glycerol to water was 3:7. 20 g of acrylamide, 30 g of trehalose, 0.1 g of LAP initiator and polyethylene glycol diacrylate were added to the system, and the molar mass ratio of the addition amount of polyethylene glycol diacrylate to acrylamide was 1:200, and gel system 2 was obtained after mixing. Gel system 2 was photocured under a 405 nm light source for 10 min to obtain a gel material.

[0053] The elastic modulus of the gel is 19 kPa, the elongation is 422%, the compression modulus is 546 kPa, the strength is 493 kPa, and the solution viscosity is 18 cp, indicating that the mechanical properties of the gel are improved with the increase of trehalose content.

[0054] Example 3

[0055] Single layer adhesive gel

[0056] 100 g of a glycerol / water mixed system was prepared, and the volume ratio of glycerol to water was 3:7. 20 g of acrylamide, 30 g of trehalose, 3 g of protocatechuic acid, 0.1 g of LAP initiator and polyethylene glycol diacrylate were added to the system, and the molar mass ratio of the addition amount of polyethylene glycol diacrylate to acrylamide was 1:500, and the gel system 3 was obtained after mixing. The gel system 3 was photocured under a 405 nm light source for 10 min to obtain a gel material.

[0057] The elastic modulus of the gel is 16kPa, the elongation is 357%, the compression modulus is 553kPa, the strength is 495kPa, and the solution viscosity is 16cp. The gel material is solidified again for 10 minutes to obtain a gel tissue compensation material, the adhesion strength with pig skin is about 4kpa, and the antibacterial rate reaches more than 95%. It shows that the addition of protocatechuic acid gives the gel adhesion properties, the adhesion strength is improved, and the gel also has antibacterial properties.

[0058] Example 4

[0059] Single layer adhesive gel

[0060] 100 g of a glycerol / water mixed system was prepared, the volume ratio of glycerol to water was 3:7, 20 g of acrylamide, 30 g of trehalose, 3 g of protocatechuic acid, 100 mg of nanoclay, 20 mg of resveratrol, 0.1 g of LAP initiator and polyethylene glycol diacrylate were added to the system, and the molar mass ratio of the addition amount of polyethylene glycol diacrylate to acrylamide was 1:500, and the gel system 4 was obtained after mixing. The gel system 4 was photocured under a 405 nm light source for 10 min to obtain a gel material.

[0061] The elastic modulus of the gel is 10kPa, the elongation is 512.3%, the compression modulus is 232kPa, the strength is 449.6kPa, and the solution viscosity is 22cp. The gel material is secondary cured for 10 minutes to obtain a gel tissue compensation material, the adhesion strength to the pig skin is about 7.5kpa, and the antibacterial rate is more than 97%. It shows that the addition of nanoclay increases the viscosity of the solution, and after loading the drug, the gel is endowed with anti-inflammatory properties.

[0062] Example 5

[0063] Double-layer asymmetric adhesive gel

[0064] Preparation of contact layer gel system: Prepare 100g of glycerol / water mixed system, the volume ratio of glycerol to water is 3:7. Add 20g of acrylamide, 30g of trehalose, 0.1g of LAP initiator and polyethylene glycol diacrylate into the system, and the molar mass ratio of the addition amount of polyethylene glycol diacrylate to acrylamide is 1:200.

[0065] Preparation of adhesion layer gel system: prepare 100g of glycerol / water mixed system, the volume ratio of glycerol to water is 3:7, add 20g of acrylamide, 30g of trehalose, 3g of protocatechuic acid, 100mg of nanoclay, 0.1g of LAP initiator and polyethylene glycol diacrylate into the system, and the molar mass ratio of the added amount of polyethylene glycol diacrylate to acrylamide is 1:600.

[0066] Take 10 ml of the contact layer gel system, use a 405 nm light source to cure for 5 seconds, add 10 ml of the adhesion layer gel system on the upper layer of the gel, and light cure for 15 minutes to obtain a gel material with asymmetric adhesion properties.

[0067] The elastic modulus of the gel was measured to be 15.6 kPa, the elongation of the gel was 267.33%, the compression modulus was 194.8 kPa, and the strength was 203.4 kPa. The adhesion strength of the double-layer gel adhesive layer to pig skin was about 9.2 kPa, and the adhesion strength of the contact layer to pig skin was about 2.4 kPa. The elastic modulus of the double-layer gel prepared at this time was similar to that of the skin.

[0068] Example 6

[0069] Double-layer asymmetric adhesive gel

[0070] Preparation of contact layer gel system: Prepare 100g of glycerol / water mixed system, the volume ratio of glycerol to water is 1:1. Add 30g of acrylamide, 30g of trehalose, 0.1g of LAP initiator and polyethylene glycol diacrylate into the system, and the molar mass ratio of the added amount of polyethylene glycol diacrylate to acrylamide is 1:100.

[0071] Preparation of adhesion layer gel system: prepare 100g of glycerol / water mixed system, the volume ratio of glycerol to water is 1:1, add 30g of acrylamide, 30g of trehalose, 6g of protocatechuic acid, 150mg of nanoclay, 0.1g of LAP initiator and polyethylene glycol diacrylate into the system, and the molar mass ratio of the added amount of polyethylene glycol diacrylate to acrylamide is 1:400.

[0072] Take 10 ml of the contact layer gel system, use a 405 nm light source to cure for 8 seconds, add 10 ml of the adhesion layer gel system on the upper layer of the gel, and light cure for 15 minutes to obtain a gel material with asymmetric adhesion properties.

[0073] The elastic modulus of the gel was measured to be 15.25 kPa, the elongation of the gel was 187.33%, the compression modulus was 194.2 kPa, and the strength was 173.6 kPa. The adhesion strength of the double-layer gel adhesive layer to pig skin was about 7.6 kPa, and the adhesion strength of the contact layer to pig skin was about 2.1 kPa. The elastic modulus of the double-layer gel prepared at this time was similar to that of the skin.

[0074] Example 7

[0075] Double-layer asymmetric adhesive gel

[0076] Preparation of contact layer gel system: Prepare 100g of glycerol / water mixed system, the volume ratio of glycerol to water is 2:3. Add 30g of acrylamide, 20g of trehalose, 0.1g of LAP initiator and polyethylene glycol diacrylate into the system, and the molar mass ratio of the polyethylene glycol diacrylate to the acrylamide is 1:50.

[0077] Preparation of adhesion layer gel system: prepare 100g of glycerol / water mixed system, the volume ratio of glycerol to water is 2:3, add 30g of acrylamide, 20g of trehalose, 5g of protocatechuic acid, 120mg of nanoclay, 0.1g of LAP initiator and polyethylene glycol diacrylate into the system, and the molar mass ratio of the added amount of polyethylene glycol diacrylate to acrylamide is 1:500.

[0078] Take 10 ml of the contact layer gel system, use a 405 nm light source to cure for 5 seconds, add 10 ml of the adhesion layer gel system on the upper layer of the gel, and light cure for 15 minutes to obtain a gel material with asymmetric adhesion properties.

[0079] The elastic modulus of the gel was measured to be 28.25 kPa, the elongation of the gel was 127.33%, the compression modulus was 204.6 kPa, and the strength was 199.2 kPa. The adhesion strength of the double-layer gel adhesive layer to pig skin was about 8 kPa, and the adhesion strength of the contact layer to pig skin was about 1.8 kPa. The elastic modulus of the double-layer gel prepared at this time was similar to that of the skin.

[0080] Example 8

[0081] Double-layer asymmetric adhesion characteristics of drug-loaded gel

[0082] The gel was prepared in the same manner as in Example 5, except that 20 mg of resveratrol was also added to the adhesive layer gel system.

[0083] Example 9

[0084] Double-layer asymmetric adhesion characteristics of drug-loaded gel

[0085] The gel was prepared in the same manner as in Example 5, except that 30 mg of curcumin was also added to the adhesive layer gel system.

[0086] Example 10

[0087] Double-layer asymmetric adhesion characteristics of drug-loaded gel

[0088] The gel was prepared in the same manner as in Example 5, except that 35 mg of allicin was also added to the adhesive layer gel system.

[0089] Embodiment 11

[0090] Personalized gel with asymmetric adhesion properties in double layers

[0091] The gel was prepared in the same manner as in Example 5, except that 20 μl of 0.2% tartrazine was added to the contact layer gel system.

[0092] Test example

[0093] The double-layer asymmetric adhesive drug-loaded gel prepared in Example 8 was applied to the exposed skin of the back of mice, and a commercial silicone bolus was used as a control group for irradiation. The single radiation dose was 10 Gy, and the radiation was performed 4 times, with an interval of more than 6 hours between two irradiations, and the irradiation was completed in 2 days. A blank group was set up, and the skin was exposed without irradiation. The skin condition of the mice was observed after one month.

[0094] One month later, the mice skin covered with the double-layer asymmetric adhesive drug-loaded gel of the present invention and the blank group showed no obvious dermatitis. In contrast, the commercial silicone bolus control group showed a certain degree of dermatitis ( Figure 6 , 7 ).

[0095] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A gel material with asymmetric adhesion properties for in vitro tissue compensators, characterized in that: including an adhesion layer and a contact layer; The adhesive layer comprises the following materials: Acrylamide, trehalose, protocatechuic acid, nanoclay, initiator, crosslinking agent and oil-water solvent, wherein the mass ratio of acrylamide, trehalose, protocatechuic acid, nanoclay and oil-water solvent in the adhesive layer is (20-30): (20-30): (3-6): (0.1-0.15): (90-110), and the molar mass ratio of the crosslinking agent to the acrylamide is 1:400-600; The contact layer comprises the following raw materials: acrylamide, trehalose, an initiator, a crosslinking agent and an oil-water solvent, wherein the mass ratio of acrylamide, trehalose and the oil-water solvent in the contact layer is (20-30): (20-40): (90-110), and the molar mass ratio of the crosslinking agent to the acrylamide is 1:50-200; The oil-water solvent is a mixture of glycerol and water, and the mass ratio of glycerol to water is (20-50): (80-50); The adhesive layer is loaded with drugs and / or dyes, and the loaded drugs are anti-inflammatory agents and / or antioxidants.

2. The gel material according to claim 1, characterized in that: The cross-linking agent includes polyethylene glycol diacrylate, and the initiator includes LAP initiator.

3. The gel material according to claim 1 or 2, characterized in that: In the adhesion layer and the contact layer, the mass ratio of the initiator to the oil-water solvent of the corresponding layer is independently 0.1:(90-110).

4. The gel material according to claim 1, characterized in that: The loaded drug is any one or more of resveratrol, curcumin, allicin and gallic acid ester.

5. A method for preparing the gel material according to any one of claims 1 to 4, characterized in that: The following steps are involved: The adhesive layer raw materials are mixed, and light-cured to an incompletely cross-linked state, and then the contact layer raw materials are mixed and placed on the adhesive layer, and secondary light-cured to obtain the gel material; or, The contact layer raw materials are mixed, and photocured once to an incompletely cross-linked state, and then the adhesive layer raw materials are mixed and placed on the contact layer, and photocured twice to obtain the gel material.

6. The preparation method according to claim 5, characterized in that: The photocuring is performed under a 405 nm light source.

7. The preparation method according to claim 5, characterized in that: The time of the first light curing is 3-5 seconds, and the time of the second light curing is more than 10 minutes.

8. Use of the gel material according to any one of claims 1 to 4 or the preparation method according to any one of claims 5 to 7 in preparing tissue compensation by 3D printing.

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