CN116036345A - Medical adhesive patch with good biocompatibility and usable in wet environment - Google Patents

Abstract

The invention discloses a medical adhesive patch with good biocompatibility, which is applicable to wet environment, wherein the main body of the patch is made of double-network hydrogel, and the surface of the hydrogel is provided with a gully-shaped microstructure; the dual network material is: a tough network composed of polyacrylamide and sodium alginate; the adhesion of the body of the adhesive patch to human skin is a topological adhesion formed by a biopolymer chitosan solution; the hydrogel patch prepared by the formula has good biocompatibility and toughness, is not easy to lose efficacy in adhesion under a wet environment, and can be firmly adhered to the skin for more than 24 hours. The present invention is conducted around three major design strategies for wet adhesion, focusing on the following three aspects: drainage property, adhesion and cohesion are realized; specifically, firstly, the surface microstructure is utilized to realize the filtration of the surface hydration film; secondly, realizing adhesiveness by covalent bonds and physical entanglement; third, tough cohesion is achieved by the dual network material.

Description

Medical adhesive patch with good biocompatibility and usable in wet environment

Technical Field

The invention belongs to the field of medical adhesive patches, and particularly relates to a medical adhesive patch with good biocompatibility and usable in a wet environment.

Background

Adhesives are any substance that can bond two materials together and prevent them from separating, and the field of biological adhesives in the biomedical field has evolved rapidly, especially in recent two years, wet adhesion has emerged in many encouraging applications in the biomedical field, such as electrodes for surgical end-suturing, for robotic crawling, with reversible adhesion actuators/grippers, tissue organ patches (e.g. heart patches), wearable sensors.

However, the traditional adhesion mechanism is single, so that the adhesion strength is insufficient, and the adhesive is easy to fail when meeting water. In particular, traditional adhesion is dependent on chemical bonding, which leads to chemical bond variability and thus adhesion failure in environments where the skin around the wound is wet for a long period of time. These deficiencies indirectly result in shortened use cycle of the adhesive patch type medical device product, bringing economic burden to the patient and inconvenience of frequent replacement. Other adhesive patches which are not prone to failure in wet environments also have drawbacks: because of the material problem, the biocompatibility is general, the skin is easy to be stimulated, and the inflammation is promoted.

Therefore, the present invention proposes three design development strategies for wet adhesion, focusing on three aspects: filtering out interfacial water, achieving adhesion and enhancing cohesion. The primary task is to remove the water at the adhesion interface, and secondly, to achieve effective adhesion in conjunction with other adhesion mechanisms, and finally, to maintain a long-lasting and firm adhesion, it is also necessary to consider how to maintain good cohesion of the material.

On the basis of the above, we propose a medical adhesive patch with good biocompatibility which is usable in wet environment.

Disclosure of Invention

The invention aims to solve the defects in the prior art, and provides a medical adhesive patch with good biocompatibility, which is usable in a wet environment, and is carried out around three design strategies of wet adhesion, wherein the three design strategies are concentrated on drainage, adhesion and cohesion, the drainage is realized by utilizing a surface microstructure, the adhesion is realized by utilizing covalent bonds and physical entanglement, and in addition, a double-network material is selected to realize tough cohesion.

In order to achieve the above purpose, the present invention provides the following technical solutions:

a biocompatible medical adhesive patch usable in a wet environment, comprising:

the patch comprises a patch main body, wherein the patch main body is made of double-network hydrogel, an adhesive is arranged on the surface, which is bonded with the skin, of the patch main body, a gully-shaped microstructure is arranged on the surface, which is bonded with the skin, of the hydrogel, and the gully-shaped microstructure is prepared by reverse molding;

the patch main body material is arranged into a double-network structure, and the double-network structure is a tough network composed of polyacrylamide and sodium alginate;

further comprises:

the patch main body is adhered to the skin of a human body by adopting topological adhesion formed by a biopolymer chitosan solution;

an absorbent layer for absorbing small amounts of blood or disinfectant present at the wound site;

preferably, an adhesive area is arranged on the patch main body, an absorption layer is arranged in the adhesive area, a release layer is arranged between the absorption layer and the adhesive area, and the surface areas of the release layer and the absorption layer are equal.

Preferably, the double-network hydrogel is formed by combining base bionic sticky hydrogel crosslinked by covalent bonds and ionic bond electrolyte hydrogel.

Preferably, the preparation steps of the ionic bond precursor solution are as follows:

and (3) mixing and dissolving anionic monomers and blue or red edible pigments in deionized water for better visualization of the samples, and stirring at room temperature until the solution is clear and transparent, or standing for 24 hours until the monomers are dissolved, so as to obtain the ionic bond electrolyte solution.

Preferably, the covalent bond cross-linking precursor solution is prepared by the following method:

and mixing and dissolving the covalent bond-crosslinkable monomer and the blue or red edible pigment in deionized water, and stirring at room temperature until the covalent bond-crosslinkable monomer and the blue or red edible pigment are fully mixed to obtain a covalent bond-crosslinkable precursor solution.

Preferably, the dual network structure includes:

and (3) a mixed solution of a polyacrylamide monomer solution and a sodium alginate monomer solution, wherein a cross-linking agent is added in the solution, and the solution is cross-linked under ultraviolet irradiation.

Preferably, the patch body further includes: crosslinking agent, accelerator, initiator and ionic crosslinking agent;

the covalent cross-linking agent is selected from N, N' -methylenediene amide (acrylamide) (MBAA, 146072-100G, 99%); the promoter is selected from N, N, N ', N' -tetramethyl ethylenediamine (TEMED, t2500-100ml,

99%); the initiator is selected from ammonium persulfate (APS, A3678-25G, 98%); the ionic crosslinker was selected from calcium sulfate (CaSO 4,255548-100G, 98%).

Preferably, the double-network structure is formed by adding a cross-linking agent, an initiator and other materials and then cross-linking by ultraviolet irradiation, wherein the preparation steps of the double-network structure are as follows:

1.000g of sodium alginate was dissolved in 25mL of distilled water for 24 hours;

5.36g of acrylamide (Aam) is taken and dissolved in 25mL of distilled water for 24 hours;

adding about 10 μl of blue or red food colorant to the solution to better visualize the gel;

preparing a mould for pouring a film, wherein the mould is made of PDMS (polydimethylsiloxane), a micro-scale gully-shaped structure which is processed is arranged on the mould, and the bottom of the mould is coated with a hydrophobic coating for lubrication so as to prevent hydrogel from adhering to the bottom of the mould;

15mL of alginate/AAm solution was taken and 600. Mu. LMBAA (0.2 g/100 mL), 100. Mu. LAPS (0.75M), 400. Mu. LCaSO4 (0.27M) and 10. Mu. LTEMED were added;

to prevent rapid gelation of the alginate and ionic crosslinker, the solution is rapidly poured into a mold; then, the gel is solidified for 1 hour under ultraviolet light (the wavelength of the ultraviolet light is 365 nm), and after the solidification is finished, the gel is soaked in distilled water for 10 minutes to release part of superfluous crosslinking agent and hydrogel;

then wrapping the aluminum foil on a glass plate, and then placing hydrogel on the aluminum foil to simplify the cutting process;

the gel was cut into pre-designed shapes in a laser cutter at 70% speed and 45% power.

Preferably, the release layer is an HDPE film, a silicone oil main agent of the release film or an additive, and the absorption layer is attached to one side of the patch main body through the release layer.

The invention has the technical effects and advantages that: compared with the traditional solid product, the medical adhesive patch with good biocompatibility and usable wet environment provided by the invention realizes drainage by utilizing a surface microstructure, realizes adhesion by utilizing covalent bonds and physical entanglement, and realizes tough cohesive force by selecting a double-network material;

secondly, the medical adhesive patch is supported by adopting double-network hydrogel, so that diffraction, reflection and attenuation effects on ultrasound under ultrasonic diagnosis frequency can not be generated when the medical adhesive patch is used as an ultrasonic patch;

in addition, when the medical adhesive patch is used as a dressing patch, a wound patch, an ostomy bag adhesive patch, a diabetic foot patch and an operation repair patch, a small amount of blood or disinfectant at a wound site and contents remained at an opening of a container are adsorbed by the absorption layer, so that inflammation and infection caused by the blood, the disinfectant and the contents on an affected part for a long time are further avoided.

Drawings

FIG. 1 shows a surface design of a gully-like micro-nano structure for an adhesive in an embodiment of the invention;

FIG. 2 is a dual network structure of an adhesive body according to an embodiment of the present invention;

FIG. 3 is a schematic diagram of adhesion achieved using dual networks and physical entanglement in an embodiment of the invention;

fig. 4 is a schematic view showing the use state of the medical adhesive patch with good biocompatibility usable in a wet environment in the embodiment of the present invention.

Detailed Description

The present invention will be described in further detail with reference to specific embodiments in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

The present invention provides a medical adhesive patch of good biocompatibility usable in the wet environment as in fig. 1 to 3, achieving an effective adhesive effect, and how to maintain the cohesive force of the adhesive material itself.

Wet adhesion solutions focus on three aspects: filtering out interfacial water, achieving adhesion and enhancing cohesion: firstly, water at an adhesion interface is removed, and effective adhesion is realized by the synergistic effect of the water and other adhesion mechanisms, finally, the following scheme is provided on the basis of eating, in order to keep long-acting firm adhesion, the better cohesive force of the material is also required to be considered:

the patch is mainly made of double-network hydrogel, and the surface of the hydrogel is provided with a gully-shaped microstructure; the dual network material is: a tough network (all that is capable of forming a double network, not limited to both) composed of polyacrylamide and sodium alginate, the double network structure comprising:

and (3) a mixed solution of a polyacrylamide monomer solution and a sodium alginate monomer solution, wherein a cross-linking agent is added in the solution, and the solution is cross-linked under ultraviolet irradiation.

The adhesion of the body of the adhesive patch to human skin is a topological adhesion formed by a solution of the biopolymer chitosan (any material capable of forming topological entanglement may be used, not limited to this material).

The hydrogel patch prepared by the formula has good biocompatibility and toughness, is not easy to lose efficacy when adhered in a wet environment, and can be firmly adhered to the skin for more than 24 hours;

the adhesion is achieved by covalent bonds and physical entanglement, and in addition, the dual-network material is selected to achieve tough cohesion;

secondly, the medical adhesive patch is supported by adopting double-network hydrogel, and can not generate diffraction, reflection and attenuation effects on ultrasound at ultrasonic diagnosis frequency when being used as an ultrasonic patch.

Further comprises:

the patch main body is adhered to the skin of a human body by adopting topological adhesion formed by a biopolymer chitosan solution;

chitosan (448869-50G, low molecular weight) and 2- (N-morpholinyl) ethanesulfonic acid (MES hydrate, M2933-25G) were used as buffers for formulating chitosan tissue adhesives. The chitosan tissue adhesive EDC-NHS includes N-hydroxysuccinimide (NHS, 130672-5G, 98%) and N- (3-dimethylaminopropyl) -N' -ethylcarbodiimide hydrochloride (EDC, 03450-1G, 98%), EDC as a cross-linking agent for chitosan.

0.476g of MES hydrate was dissolved in 50.0mL H2O. The pH is about 5 to about 6. Then 0.5g chitosan was dissolved into the MES hydrate solution for 1 hour to be thoroughly mixed. The solution was then covered and left to stand for 24 hours to release the remaining bubbles in the solution. The solution was slightly viscous and pale yellow.

The tissue adhesive EDC-NHS was prepared to give NHS and EDC at a concentration of 12 mg/mL. In this case, 0.12gNHS was weighed and mixed in 5mL chitosan/MES buffer, and 0.12gEDC was mixed into another 5mL chitosan/MES buffer as previously described to prevent cross-linking of NHS and EDC prior to adhesive application. The solution was then covered and left to stand for 24 hours. The solution was viscous but more clear than the previously described solutions. When in use, the two liquids are respectively dripped on the places where the two liquids are required to be adhered.

The absorption layer is used for absorbing a small amount of blood or disinfectant which appears at a wound and contents which remain at an opening of the container, the adhesive area is arranged on the patch main body, the absorption layer is arranged in the adhesive area, the release layer is arranged between the absorption layer and the adhesive area, and the surface areas of the release layer and the absorption layer are equal;

the release layer is an HDPE film, a silicone oil main agent of the release film or an additive, and the absorption layer is attached to one side of the patch main body through the release layer.

When the medical adhesive patch is used as a dressing patch, a wound patch, an ostomy bag adhesive patch, a diabetic foot patch and an operation repair patch, the absorbent layer is used for absorbing a small amount of blood or disinfectant appearing at a wound and the content remained at the opening of the container, so that inflammation and infection caused by the blood, the disinfectant and the content on the long-time basis of the affected part are further avoided.

It is worth to say that the double-network hydrogel is composed of a base bionic sticky hydrogel crosslinked by covalent bonds and an ionic bond electrolyte hydrogel.

Further, the preparation of the ionomer electrolyte hydrogel is not as follows:

the preparation steps of the ionic bond precursor solution are as follows:

and (3) mixing and dissolving anionic monomers and blue or red edible pigments in deionized water for better visualization of the samples, and stirring at room temperature until the solution is clear and transparent, or standing for 24 hours until the monomers are dissolved, so as to obtain the ionic bond electrolyte solution.

5. A wet environmentally friendly biocompatible medical adhesive patch according to claim 3, wherein: the preparation method of the covalent bond crosslinking precursor solution comprises the following steps:

and mixing and dissolving the covalent bond-crosslinkable monomer and the blue or red edible pigment in deionized water, and stirring at room temperature until the covalent bond-crosslinkable monomer and the blue or red edible pigment are fully mixed to obtain a covalent bond-crosslinkable precursor solution.

The patch main body further comprises: crosslinking agent, accelerator, initiator and ionic crosslinking agent;

the covalent cross-linking agent is selected from N, N' -methylenediene amide (acrylamide) (MBAA, 146072-100G, 99%); the promoter is selected from N, N, N ', N' -tetramethyl ethylenediamine (TEMED, t2500-100ml,

99%); the initiator is selected from ammonium persulfate (APS, A3678-25G, 98%); the ionic crosslinker was selected from calcium sulfate (CaSO 4,255548-100G, 98%).

In this embodiment, the dual-network structure includes:

a polyacrylamide grid;

the preparation flow of the polyacrylamide grid is as follows:

the double-network structure is formed by adding cross-linking agent, initiator and other materials into a polymer material capable of forming ionic bonds and a polymer material capable of forming covalent bonds and then cross-linking the polymer material under ultraviolet irradiation, and the preparation steps of the double-network structure are as follows:

1.000g of sodium alginate was dissolved in 25mL of distilled water for 24 hours;

5.36g of acrylamide (Aam) is taken and dissolved in 25mL of distilled water for 24 hours;

adding about 10 μl of blue or red food colorant to the solution to better visualize the gel;

preparing a mould for pouring a film, wherein the mould is made of PDMS (polydimethylsiloxane), a micro-scale gully-shaped structure which is processed is arranged on the mould, and the bottom of the mould is coated with a hydrophobic coating for lubrication so as to prevent hydrogel from adhering to the bottom of the mould;

15mL of alginate/AAm solution was taken and 600. Mu. LMBAA (0.2 g/100 mL), 100. Mu. LAPS (0.75M), 400. Mu. LCaSO4 (0.27M) and 10. Mu. LTEMED were added;

to prevent rapid gelation of the alginate and ionic crosslinker, the solution is rapidly poured into a mold; then, the gel is solidified for 1 hour under ultraviolet light (the wavelength of the ultraviolet light is 365 nm), and after the solidification is finished, the gel is soaked in distilled water for 10 minutes to release part of superfluous crosslinking agent and hydrogel;

then wrapping the aluminum foil on a glass plate, and then placing hydrogel on the aluminum foil to simplify the cutting process;

the gel was cut into pre-designed shapes in a laser cutter at 70% speed and 45% power.

Finally, it should be noted that: the foregoing description is only illustrative of the preferred embodiments of the present invention, and although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described, or equivalents may be substituted for elements thereof, and any modifications, equivalents, improvements or changes may be made without departing from the spirit and principles of the present invention.

Claims (9)

1. A biocompatible medical adhesive patch usable in a wet environment, comprising:

the patch comprises a patch main body, wherein the patch main body is made of double-network hydrogel, an adhesive is arranged on the surface, which is bonded with the skin, of the patch main body, a gully-shaped microstructure is arranged on the surface, which is bonded with the skin, of the hydrogel, and the gully-shaped microstructure is prepared by reverse molding;

the patch main body material is arranged into a double-network structure, and the double-network structure is a tough network composed of polyacrylamide and sodium alginate;

further comprises:

the patch main body is adhered to the skin of a human body by adopting topological adhesion formed by a biopolymer chitosan solution;

an absorbent layer for absorbing small amounts of blood or disinfectant present at the wound site.

2. A wet environmentally friendly biocompatible medical adhesive patch according to claim 1, wherein: the patch body is provided with an adhesive area, an absorption layer is arranged in the adhesive area, a release layer is arranged between the absorption layer and the adhesive area, and the surface areas of the release layer and the absorption layer are equal.

3. A wet environmentally friendly biocompatible medical adhesive patch according to claim 1, wherein: the double-network hydrogel is formed by combining base bionic sticky and tough hydrogel crosslinked by covalent bonds and ionic bond electrolyte hydrogel.

4. A wet environmentally friendly biocompatible medical adhesive patch according to claim 3, wherein: the preparation steps of the ionic bond precursor solution are as follows:

and (3) mixing and dissolving anionic monomers and blue or red edible pigments in deionized water for better visualization of the samples, and stirring at room temperature until the solution is clear and transparent, or standing for 24 hours until the monomers are dissolved, so as to obtain the ionic bond electrolyte solution.

5. A wet environmentally friendly biocompatible medical adhesive patch according to claim 3, wherein: the preparation method of the covalent bond crosslinking precursor solution comprises the following steps:

and mixing and dissolving the covalent bond-crosslinkable monomer and the blue or red edible pigment in deionized water, and stirring at room temperature until the covalent bond-crosslinkable monomer and the blue or red edible pigment are fully mixed to obtain a covalent bond-crosslinkable precursor solution.

6. A wet environmentally friendly biocompatible medical adhesive patch according to claim 1, wherein: the dual network architecture includes:

and (3) a mixed solution of a polyacrylamide monomer solution and a sodium alginate monomer solution, wherein a cross-linking agent is added in the solution, and the solution is cross-linked under ultraviolet irradiation.

7. The wet environmentally friendly biocompatible medical adhesive patch according to claim 6, wherein: the patch main body further comprises: crosslinking agent, accelerator, initiator and ionic crosslinking agent;

the covalent cross-linking agent is selected from N, N' -methylene diene amide; the accelerator is N, N, N ', N' -tetramethyl ethylenediamine; the initiator is ammonium persulfate; the ionic crosslinking agent is calcium sulfate.

8. The wet environmentally friendly biocompatible medical adhesive patch according to claim 7, wherein: the double-network structure is formed by adding cross-linking agent, initiator and other materials into a polymer material capable of forming ionic bonds and a polymer material capable of forming covalent bonds and then cross-linking the polymer material under ultraviolet irradiation, and the preparation steps of the double-network structure are as follows:

1.000g of sodium alginate was dissolved in 25mL of distilled water for 24 hours;

5.36g of acrylamide is taken and dissolved in 25mL of distilled water for 24 hours;

adding about 10 μl of blue or red food colorant to the solution to better visualize the gel;

preparing a mould for pouring a film, wherein the mould is made of PDMS, a micro-scale gully-shaped structure which is processed is arranged on the mould, and the bottom of the mould is coated with a hydrophobic coating for lubrication so as to prevent a hydrogel from adhering to the bottom of the mould;

15mL of alginate/AAm solution was taken and 600. Mu.LMBAA, 100. Mu.LAPS, 400. Mu.LCaSO 4 and 10. Mu.LTEMED were added;

to prevent rapid gelation of the alginate and ionic crosslinker, the solution is rapidly poured into a mold; then, the gel is solidified for 1 hour under ultraviolet light, and after the solidification is finished, the gel is soaked in distilled water for 10 minutes to release part of superfluous crosslinking agent and hydrogel;

then wrapping the aluminum foil on a glass plate, and then placing hydrogel on the aluminum foil to simplify the cutting process;

the gel was cut into pre-designed shapes in a laser cutter at 70% speed and 45% power.

9. A wet environmentally compatible medical adhesive patch according to claim 2, wherein: the release layer is an HDPE film, a silicone oil main agent of the release film or an additive, and the absorption layer is attached to one side of the patch main body through the release layer.

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