CN114949331B - Double-bionic dry type tissue adhesive patch capable of rapidly stopping bleeding and easing pain and preparation method thereof - Google Patents
Double-bionic dry type tissue adhesive patch capable of rapidly stopping bleeding and easing pain and preparation method thereof Download PDFInfo
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A61L2400/00—Materials characterised by their function or physical properties
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Abstract
The invention discloses a double-bionic dry type rapid hemostatic and analgesic tissue adhesive patch and a preparation method thereof, wherein the method comprises the following steps: preparing a hydrogel material of mussel bionic components; preparing a precursor solution of the composite tissue adhesive; preparing a male die template of an octopus sucking disc bionic structure; and adding the precursor solution of the composite tissue adhesive to the male die template of the octopus sucker bionic structure, and irradiating and crosslinking to prepare the patch. The preparation method of the invention has mild conditions, the preparation process is nontoxic and harmless, the double-bionic dry-type rapid hemostasis and analgesia tissue adhesive patch prepared by the preparation method has high safety and bioactivity, controllable biodegradation, no pollution to the environment, good flexibility and mechanical strength, convenient carrying, rapid realization of hemostasis and analgesia effects, high drug and growth factor loading capacity, and tissue repair while hemostasis and analgesia are realized by controlling the in vivo degradability of the tissue adhesive.
Description
Technical Field
The invention relates to the field of bionic medical tissue adhesives, in particular to a double-bionic dry type rapid hemostatic and analgesic tissue adhesive patch and a preparation method thereof.
Background
Uncontrolled blood loss is a significant cause of war and peaceful time trauma death. In the field environment, such as daily military training, war, fire control, natural disasters, safety accidents and the like, the death probability of the wounded is greatly increased due to the lack of effective rescue facilities and time urgency in the bleeding site. Pain is another important factor which endangers the life of a wounded person, and a large amount of pain-causing substances are generated due to pain caused by trauma, so that the pain has serious influence on the vascular permeability and the diastolic degree of the wounded person and the heart rate of the wounded person. According to statistics, the bleeding and death probability of the wounded in special tasks and extremely severe environments is over 90%, and the probability that the casualties die of local uncontrollable bleeding and pain is over 50% can be avoided. At present, the research on the hemostatic materials at home and abroad is slightly laggard, and the hemostatic materials used in the traditional clinical surgery, such as chitosan-based powder, gelatin-based hemostatic powder, oxidized cellulose, fibrin adhesive and the like, are mainly researched and developed at present, but the materials have no analgesic effect, have poor adhesion performance with moist trauma tissues and are difficult to meet the requirement of rapid adhesion hemostasis in complex environments. In summary, hemostatic materials currently face serious challenges: 1) The hemostatic material has single function, lacks adhesiveness and analgesic performance, has complex use steps, needs secondary operation and has poor patient compliance; 2) The material has short shelf life and is inconvenient to carry; 3) Outdoor emergency hemostasis is limited.
The tissue adhesive is a novel material which replaces the traditional operation suture, rivet and mechanical fixing method and is applied to the rapid wound closure and hemostasis, mainly comprises flexible hydrogel molecules and can be adhered to wound tissues through a series of physical and chemical actions. The tissue adhesive has the advantages of simple operation, noninvasive closure, high water content, controllable degradation, capability of stanching, pain reduction, antibiosis and the like, and is expected to be a novel hemostatic material for surgery. Although there are some tissue adhesives (such as fibrin and cyanoacrylate) in clinical application, the current biomedical tissue adhesives have the challenges of low adhesion strength of wet tissue surface, high biosafety risk, poor hemostatic effect, etc., and are difficult to satisfy the hemostatic and analgesic requirements of the wounded in clinical surgery and field environments, especially difficult to be applied to hemostasis of trauma of the wounded in military operations and extremely harsh environments.
Accordingly, the prior art is yet to be improved and developed.
Disclosure of Invention
In view of the defects of the prior art, the invention aims to provide a double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch and a preparation method thereof, and aims to solve the problems of low adhesion strength, high biosafety risk and poor hemostatic effect of the conventional biomedical tissue adhesive on the surface of a wet tissue.
The technical scheme adopted by the invention for solving the technical problems is as follows:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
dissolving photo-crosslinkable natural high polymer material powder in a PBS (phosphate buffer solution), stirring until the photo-crosslinkable natural high polymer material powder is dissolved, adding EDC, NHS and micromolecules containing a phenol structure, stirring for reaction, dialyzing, and freeze-drying to obtain a mussel bionic component hydrogel material;
mixing a hydrogel material of the mussel bionic components and gelatin powder, dissolving the mixture in a PBS solution, activating at room temperature, adding an inorganic hemostatic agent, a water-soluble local analgesic and a photoinitiator, and stirring to obtain a precursor solution of the composite tissue adhesive;
designing a bionic geometric structure, and constructing a bionic structure array on the surface of the hard substrate according to the bionic geometric structure to obtain an octopus sucking disc bionic structure male die template;
and adding the composite tissue adhesive precursor solution to the octopus sucking disc bionic structure male die template, irradiating for crosslinking, and drying to obtain the double bionic dry type rapid hemostasis and analgesia tissue adhesive patch.
The preparation method of the double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch comprises the steps of preparing a photo-crosslinkable natural high polymer material, and preparing a methacryloylated natural high polymer material from one of methacryloyl gelatin, methacryloyl hyaluronic acid, sodium methacryloyl alginate, methacryloyl silk fibroin and methacryloyl chondroitin sulfate.
The preparation method of the double-bionic dry-type tissue adhesive patch capable of rapidly stopping bleeding and easing pain comprises the steps of enabling the pH value of a PBS solution to be 4-5, and enabling small molecules containing a phenol structure to be one or more of dopamine hydrochloride, levodopa, gallic acid, galloaldehyde and trihydroxybenzoyl.
The preparation method of the double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the step of preparing a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch, wherein the inorganic hemostatic agent is one or more of calcium carbonate, calcium chloride, aluminum potassium sulfate and ferric chloride.
The preparation method of the double-bionic dry tissue adhesive patch for rapidly stopping bleeding and easing pain comprises the step of preparing a local analgesic, wherein the local analgesic is one or more of lidocaine, bupivacaine, ropivacaine, tetracaine, procaine, chloroprocaine and ketorolac tromethamine.
The preparation method of the double bionic dry type rapid hemostatic and analgesic tissue adhesive patch comprises the step of preparing a photoinitiator, wherein the photoinitiator is phenyl-2, 4, 6-trimethyl lithium benzoylphosphonate or Pasteur Irgacure2959.
The preparation method of the double-bionic dry type rapid hemostasis and analgesia tissue adhesive paster comprises the following steps of designing a bionic geometric structure, constructing a bionic structure array on the surface of a hard substrate according to the bionic geometric structure, and obtaining a male die template of an octopus sucker bionic structure, wherein the step comprises the following steps:
designing a bionic geometric structure of the octopus sucker based on a CAD drawing method;
constructing a bionic structure array on the surface of the hard substrate according to the bionic geometric structure by utilizing an advanced manufacturing technology to obtain an octopus sucking disc bionic structure male die template;
wherein the advanced manufacturing technology comprises one or more of a photocuring 3D printing technology, a fused deposition 3D printing technology, a precise numerical control milling technology and a laser engraving technology.
The preparation method of the double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the step of preparing a hard base material, wherein the hard base material is one of aluminum alloy, copper alloy, polymethyl methacrylate and glass.
The preparation method of the double-bionic dry type rapid hemostasis and analgesia tissue adhesive paster comprises the following steps of adding the composite tissue adhesive precursor solution to the octopus sucking disc bionic structure male die template, irradiating for crosslinking, and drying to obtain the double-bionic dry type rapid hemostasis and analgesia tissue adhesive paster, wherein the steps comprise:
preheating the male die template of the octopus sucker bionic structure at 50 ℃ for 5-10min;
and adding the composite tissue adhesive precursor solution to a preheated male die template with an octopus sucking disc bionic structure, placing a pressing sheet above the template, decompressing and removing bubbles, irradiating and crosslinking for 10-60s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostatic-analgesic tissue adhesive patch.
The double-bionic dry type rapid hemostasis and analgesia tissue adhesive paster prepared by the method comprises an octopus sucking disc bionic structure male die template and hydrogel which is arranged on the octopus sucking disc bionic structure male die template and is modified with mussel bionic components with a phenol micromolecule structure.
Has the beneficial effects that: the invention discloses a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch and a preparation method thereof, aiming at the problems of poor blood coagulation effect, high price, no analgesia effect, difficult storage, complex use and the like of the existing hemostasis material, the invention designs a synergistic structure of mussel-like catechol and an octopus-like sucker based on the bionics principle, and greatly improves the tissue adhesion strength of the dry type tissue adhesive patch. The beneficial effect generated by the components of the material is remarkable, wherein the catechol active molecular structure of the mussel can perform a series of chemical reactions with amino groups and other groups on the surface of a tissue under a humid condition, so that a durable strong tissue adhesion force is generated, and the tissue adhesive is endowed with the moisture-resistant bonding performance; furthermore, a patterned octopus-imitated sucker micro-nano structure is constructed on the surface of the tissue adhesive, so that the rapid initial adhesion strength of the tissue adhesive is realized. The addition of inorganic hemostatic has an important role in promoting physiological hemostasis, and the released inorganic cations cause waterfall type physiological coagulation reaction through the steps of activating platelets to activate thrombin and the like, so that the inorganic hemostatic is one of the most proven in vivo hemostasis mechanisms at present. The local anesthetic added in the patch is a local anesthetic commonly used in clinical surgery, has low side effect and does not generate action inhibition, but has limited effective analgesic time of injection administration. The project endows the material with the functions of rapid hemostasis and long-acting analgesia by optimizing the preparation method and the controllable release process of the tissue adhesive loaded nano inorganic hemostatic and the local anesthetic. The developed dry tissue adhesive paster integrates strong tissue adhesion, rapid hemostasis and long-acting analgesia, is convenient to carry, and can be used after being pasted. In addition, the preparation method of the invention has mild conditions, the preparation process is non-toxic and harmless, and the double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch prepared by the preparation method of the invention has high safety and bioactivity, controllable biodegradation and no pollution to the environment. The prepared tissue adhesive patch has good flexibility and mechanical strength, can quickly realize the effects of stopping bleeding and easing pain, has high drug and growth factor loading capacity, and can repair tissues while stopping bleeding and easing pain by controlling the degradability of the tissue adhesive in vivo.
Drawings
Fig. 1 is a flow chart of an implementation of a method for preparing a double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch provided by the invention;
FIG. 2 is a physical diagram of an octopus sucking disc bionic structure male die template obtained based on an advanced manufacturing technology;
FIG. 3 is a schematic view of the preparation of a double-bionic dry-type rapid hemostatic analgesic tissue adhesive patch of the present invention;
FIG. 4 is a graph of the thickness variation of tissue adhesive patches prepared with different concentrations of calcium carbonate hemostatic additive in accordance with the present invention;
FIG. 5 shows the tensile strength results of the double biomimetic tissue adhesive patch prepared in accordance with the present invention;
FIG. 6 is a graph showing the morphology of a double-bionic dry-type rapid hemostatic-analgesic tissue adhesive patch and surface bionic pores prepared according to the present invention;
FIG. 7 is a diagram of the adhesion and wound closure effect of the double bionic dry type rapid hemostatic and analgesic tissue adhesive patch of the present invention on different tissue surfaces;
fig. 8 is a real diagram of the hemostatic and adhesive effects of the double-bionic dry-type rapid hemostatic-analgesic tissue adhesive patch of the present invention in a rat liver acute hemorrhage model.
Detailed Description
The invention provides a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch and a preparation method thereof, and the invention is further explained in detail below in order to make the purpose, technical scheme and effect of the invention clearer and clearer. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The tissue adhesive is a novel material which replaces the traditional operation suture, rivet and mechanical fixing method and is applied to the rapid closing and hemostasis of wounds, mainly consists of flexible hydrogel molecules and can be adhered to wound tissues through a series of physical and chemical actions. The tissue adhesive has the advantages of simple operation, noninvasive closure, high water content, controllable degradation, capability of stopping bleeding, reducing pain, antibiosis and the like, and is expected to be a novel surgical hemostatic material. Although there are some tissue adhesives (e.g. fibrin, cyanoacrylate) in clinical application, the current biomedical tissue adhesives have the challenges of low adhesion strength of wet tissue surface, high biosafety risk, and poor hemostatic effect, and are difficult to satisfy the hemostatic and analgesic requirements of the wounded in clinical surgery and field environments, especially difficult to be applied to hemostasis of trauma of wounded in military operations and extremely harsh environments. The design and development of a novel rapid adhesion, hemostasis and long-acting analgesia integrated instant-use multifunctional portable dry tissue adhesive is the development direction of the military and civil medical emergency hemostasis material at present. The natural polymer biomaterial has larger application potential, and the development of a new generation of hemostatic and analgesic adhesive material based on the methacrylated hydrogel material with excellent biocompatibility and rapid photocuring capability has larger application value.
Based on the above, referring to fig. 1-3, the invention provides a preparation method of a double-bionic dry type rapid hemostatic and analgesic tissue adhesive patch, which comprises the following steps:
s10, dissolving photo-crosslinkable natural polymer material powder in a PBS solution, stirring until the photo-crosslinkable natural polymer material powder is dissolved, adding EDC, NHS and micromolecules containing a phenol structure, stirring for reaction, dialyzing, and freeze-drying to obtain a hydrogel material of the bionic components of the mussel;
s20, mixing a hydrogel material of the mussel bionic component and gelatin powder, dissolving the mixture in a PBS solution, activating at room temperature, adding an inorganic hemostatic agent, a water-soluble local analgesic and a photoinitiator, and stirring to obtain a precursor solution of the composite tissue adhesive;
s30, designing a bionic geometric structure, and constructing a bionic structure array on the surface of the hard substrate according to the bionic geometric structure to obtain a male die template of the bionic structure of the octopus sucker;
s40, adding the composite tissue adhesive precursor solution to the octopus sucker bionic structure male die template, irradiating, crosslinking and drying to obtain the double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch.
The preparation method provided by the invention has the advantages that the components of the mussel material are bionic by chemically modifying a phenol micromolecule structure on a natural hydrogel macromolecule, the octopus sucker bionic structure is prepared by a template method, the process is simple, the preparation cost is low, the conditions are mild, and the preparation process is non-toxic and harmless.
In some embodiments, the photo-crosslinkable natural polymer material is a methacrylated natural polymer material, and the methacrylated natural polymer material is one of methacrylated gelatin (GelMA), methacrylated hyaluronic acid (HAMA), methacrylated sodium alginate (AlgMA), methacrylated silk fibroin (SilMA), and methacrylated chondroitin sulfate (ChsMA). The materials are all derived from modification of natural biological materials, the main component is a polysaccharide material, the biological safety is high, and the photo-crosslinking material has quick photo-crosslinking property.
In some embodiments, the PBS solution has a pH of 4 to 5, the excess of the peracid affects the yield and the effect of the reaction, and the small molecule containing the phenol structure is one or more of dopamine hydrochloride, levodopa, gallic acid, gallic aldehyde and trihydroxybenzoyl, and the materials have the mussel-simulated catechol structure, so as to provide the materials with good adhesion.
In some embodiments, the step S10 is specifically: dissolving photo-crosslinkable natural high polymer material powder in PBS (phosphate buffer solution) with the pH value of 4-5, stirring at 50 ℃ until the photo-crosslinkable natural high polymer material powder is dissolved to obtain 1-5% by mass volume of hydrogel solution, adding 0.1-1% by mass volume of EDC and 0.1-0.6% by mass volume of NHS (polyethylene glycol succinate) at the set rotating speed of 300-500rpm, activating at room temperature for 30-60min, adding small molecules containing a phenol structure, stirring at 37 ℃, reacting for 12-24h, dialyzing, and freeze-drying to obtain the hydrogel material with the mussel bionic components.
In some embodiments, the inorganic hemostatic agent is one or more of calcium carbonate, calcium chloride, potassium aluminum sulfate, and ferric chloride, which are capable of slowly releasing cations to activate physiological coagulation mechanisms.
Preferably, in this embodiment, the inorganic hemostatic agent is calcium carbonate, in order to study the performance influence of calcium carbonate on the double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch, the addition of calcium carbonate is tested, and the test results are shown in fig. 4 and 5, as can be seen from the figures, the thickness of the double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch can be controlled by adjusting the concentration and the addition amount of calcium carbonate, and the tensile strength of the double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch can be greatly improved by adding the nano calcium carbonate hemostatic agent.
In some embodiments, the local analgesic is one or more of lidocaine, bupivacaine, ropivacaine, tetracaine, procaine, chloroprocaine and ketorolac tromethamine, and the anesthetic is a local anesthetic with high safety, fast anesthetic effect and small side effect.
In some embodiments, the photoinitiator is lithium phenyl-2, 4, 6-trimethylbenzoylphosphonate or basf Irgacure2959, which is less cytotoxic and can rapidly crosslink under blue light irradiation.
Optionally, in the step S20, the stirring temperature is 50 ℃ and the stirring time is 1-2h, and the temperature and the stirring time ensure that the material is uniformly compounded, and simultaneously ensure the high activity of the anesthetic and the integrity of the inorganic hemostatic agent.
In some embodiments, the step of designing a bionic geometric structure, and constructing a bionic structure array on the surface of the hard substrate according to the bionic geometric structure to obtain the male mold template of the bionic structure of the octopus sucker comprises the steps of:
designing an octopus sucking disc bionic geometric structure based on a CAD drawing method;
constructing a bionic structure array on the surface of the hard substrate according to the bionic geometric structure by utilizing an advanced manufacturing technology to obtain an octopus sucking disc bionic structure male die template;
the advanced manufacturing technology comprises one or more of a photocuring 3D printing technology, a melting and stacking 3D printing technology, a precise numerical control milling technology and a laser engraving technology, the 3D printing technology has the advantages of high preparation speed, high precision, low cost and the like, and as shown in figure 2, the invention is an octopus sucker bionic structure male die template real object diagram obtained based on the advanced manufacturing technology.
In some embodiments, the hard substrate is one of aluminum alloy, copper alloy, polymethyl methacrylate and glass, and the materials have moderate hardness and good processability, and have low deformation amount during heating, so that the shape fidelity of the structure in the subsequent reverse molding process is ensured.
Optionally, the biomimetic structure array can be processed into different sizes and shapes according to actual requirements, the shape of a single biomimetic structure can be circular, triangular, rectangular or rhombic, and the surface area of the single biomimetic structure is 0.0025-0.25mm 2 And the height is 50-200 μm, the distance between each bionic structure in the bionic structure array is equal and is 100-300 μm, the sizes are size ranges processed by advanced manufacturing technology, and the mechanical strength and the tissue adhesion force of the tissue adhesive patch are not influenced, referring to fig. 6, the double bionic dry type rapid hemostasis and analgesia tissue adhesive patch and the surface bionic pore morphology graph are prepared for the invention, in the embodiment, the shape of each single bionic structure is a hexagon, and the side length of the hexagon is 400 μm.
In some embodiments, the step of adding the composite tissue adhesive precursor solution to the octopus sucking disc bionic structure male mold template, irradiating for crosslinking, and drying to obtain the double bionic dry type rapid hemostatic and analgesic tissue adhesive patch comprises the steps of:
preheating the octopus sucking disc bionic structure male die template for 5-10min at 50 ℃, wherein the preheated template ensures that the tissue adhesive can be uniformly spread on the surface of the template;
adding the composite tissue adhesive precursor solution to a preheated octopus sucking disc bionic structure male die template, placing a pressing sheet above the template, decompressing and removing bubbles, irradiating and crosslinking for 10-60s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double bionic dry type rapid hemostasis and analgesia tissue adhesive patch, wherein the mechanical strength of the tissue adhesive patch is insufficient when the crosslinking time is less than 10s, and the brittleness of the tissue adhesive patch prepared when the crosslinking time is more than 60s is large.
In the embodiment, the thickness of the prepared double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch is 10-300 μm, and the thickness meets the hemostasis condition, so that the tissue adhesive material can be completely degraded in one month in vivo, and the tissue ingrowth material is facilitated.
The invention also provides a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch prepared by the method in the scheme, as shown in figure 2, the patch 3 comprises an octopus sucking disc bionic structure male mold template 1 and hydrogel 2 which is arranged on the octopus sucking disc bionic structure male mold template and is modified with mussel bionic components with a phenol micromolecule structure.
The double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch prepared by the invention has better biocompatibility and controllable degradability, can rapidly realize rapid adhesion with wet tissues, and has high tissue adhesion strength; the hemostatic powder is applied to the field of trauma first aid of field personnel, and has the integrated treatment functions of rapid hemostasis and long-acting analgesia; the tissue adhesive dry type patch has good flexibility and long shelf life, is convenient to carry, can be used as a first-aid product for field traumatic hemorrhage after being pasted and used immediately.
In some embodiments, the use method of the double bionic dry type rapid hemostasis and analgesia tissue adhesive patch is as follows:
tearing the double-bionic dry-type rapid hemostasis and analgesia tissue adhesive patch from the surface of the male die template of the octopus sucker bionic structure, then carrying out sterilization treatment, carrying out personalized cutting according to the using part and the wound size, then attaching the patch to the skin bleeding wound part of the trunk and the limbs or the liver, heart, spleen or artery injury part, and pressing for 10-30s, thus realizing strong tissue adhesion, hemostasis and analgesia effects.
The technical solution in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. It is clear that the described embodiments are only a part of the embodiments of the invention, not all embodiments, merely intended to illustrate the invention and in no way limit it. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
(A) Preparing a hydrogel material of mussel bionic components: dissolving GelMA powder in PBS solution with pH of 4.5, stirring at 50 deg.C to dissolve, obtaining GelMA solution with concentration of 2%, adding 0.5% EDC and 0.3% NHS,500rpm, activating at room temperature for 30min, adding dopamine hydrochloride with final concentration of 1.5%, stirring at 37 deg.C for 24 hr, dialyzing, and freeze drying;
(B) Preparing a precursor solution of the composite tissue adhesive: dissolving the hydrogel material and gelatin powder of the mussel bionic component in the step (A) in PBS according to a certain proportion, respectively preparing 10% and 20% gel solutions, then adding an inorganic hemostatic calcium carbonate, a water-soluble local analgesic ropivacaine and a photoinitiator, namely phenyl-2, 4, 6-trimethylbenzoyllithium phosphonate, and stirring for 1h at 50 ℃;
（C）processing a male die template of the octopus sucker bionic geometric structure: designing a bionic geometric structure based on a CAD drawing method, and constructing the surface area of a single bionic structure on the surface of the copper alloy base material by utilizing a precise numerical control milling technology to be 0.1mm 2 A rhombic bionic structure array with the height of 100 mu m and the array interval of 100 mu m;
(D) Preparing a double-bionic dry tissue adhesive patch: slowly adding the precursor solution of the composite tissue adhesive prepared in the step (B) into the bionic structure template preheated at 50 ℃ for 10min, slightly placing a polydimethylsiloxane tabletting above the template, decompressing to remove bubbles for 60s, irradiating and crosslinking for 10-60s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostatic and analgesic tissue adhesive patch with the thickness of 300 mu m.
Example 2:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
(A) Preparing a hydrogel material of mussel bionic components: dissolving HAMA powder in PBS (pH 4), stirring at 50 deg.C to dissolve to obtain 1% HAMA solution, adding 0.1% EDC and 0.1% NHS at the same time, 300rpm, activating at room temperature for 60min, adding levodopa with final concentration of 0.5%, stirring at 37 deg.C for 12 hr, dialyzing, and freeze drying;
(B) Preparing a precursor solution of the composite tissue adhesive: dissolving the hydrogel material and gelatin powder of the mussel bionic component in the step (A) in PBS according to a certain proportion, respectively preparing 5% and 10% gel solutions, then adding an inorganic hemostatic calcium chloride, a water-soluble local analgesic lidocaine and a photoinitiator Basfer Irgacure2959, and stirring for 2h at 50 ℃;
(C) Processing a male die template of the octopus sucker bionic geometric structure: based on a CAD drawing method, a bionic geometric structure is designed, and the surface area of a single bionic structure is constructed on the surface of the aluminum alloy substrate by utilizing the photocuring 3D printing technology, wherein the surface area is 0.0025mm 2 A circular bionic structure array with the height of 50 mu m, wherein the array interval is 150 mu m;
(D) Preparing a double bionic dry tissue adhesive patch: slowly adding the composite tissue adhesive precursor solution prepared in the step (B) into the bionic structure template preheated at 50 ℃ for 5min in the step (C), slightly placing a glass pressing sheet above the bionic structure template, decompressing to remove bubbles for 60s, irradiating and crosslinking for 10s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostatic-analgesic tissue adhesive patch with the thickness of 100 mu m.
Example 3:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
(A) Preparation of hydrogel material of mussel bionic component: dissolving AlgMA powder in PBS with pH of 5, stirring at 50 deg.C until dissolved to obtain AlgMA solution with concentration of 5%, adding 1% EDC and 0.6% NHS simultaneously, 400rpm, activating at room temperature for 40min, adding trihydroxybenzoyl with final concentration of 2%, vigorously stirring at 37 deg.C for 16h, dialyzing, and freeze drying;
(B) Preparing a precursor solution of the composite tissue adhesive: dissolving the hydrogel material and gelatin powder of the mussel bionic component in the step (A) in PBS according to a certain proportion, respectively preparing gel solutions with the concentration of 8% and 15%, then adding an inorganic hemostatic potassium aluminum sulfate, a water-soluble local analgesic bupivacaine and a photoinitiator phenyl-2, 4, 6-trimethylbenzoyllithium phosphonate, and stirring for 1.5h at 50 ℃;
(C) Processing a male die template of the octopus sucker bionic geometric structure: designing a bionic geometric structure based on a CAD drawing method, and constructing the surface area of a single bionic structure on the surface of a glass substrate by utilizing a fusion stacking 3D printing technology to be 0.25mm 2 A triangular bionic structure array with the height of 200 mu m, wherein the array interval is 300 mu m;
(D) Preparing a double bionic dry tissue adhesive patch: slowly adding the composite tissue adhesive precursor solution prepared in the step (B) into the bionic structure template preheated at 50 ℃ for 8min in the step (C), slightly placing a polymethyl methacrylate tablet above the bionic structure template, decompressing and removing bubbles for 60s, irradiating and crosslinking for 30s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch with the thickness of 500 mu m.
Example 4:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
(A) Preparing a hydrogel material of mussel bionic components: dissolving ChsMA powder in PBS with pH of 4.3, stirring at 50 deg.C to dissolve to obtain 3% ChsMA solution, adding 0.3% EDC and 0.2% NHS,350rpm simultaneously, activating at room temperature for 50min, adding dopamine hydrochloride with final concentration of 1%, vigorously stirring at 37 deg.C for 20h, dialyzing, and freeze drying;
(B) Preparing a precursor solution of the composite tissue adhesive: dissolving the hydrogel material and gelatin powder of the mussel bionic component in the step (A) in PBS according to a certain proportion, respectively preparing gel solutions with the concentration of 6% and 12%, then adding inorganic hemostatic agents of ferric chloride, water-soluble local analgesic agents of tetracaine and Bassfer Irgacure2959, and stirring for 1.5h at 50 ℃;
(C) Processing a male die template of the octopus sucker bionic geometric structure: based on CAD drawing method, bionic geometric structure is designed, laser carving technology is utilized, and surface area of single bionic structure is 0.001mm 2 A rectangular bionic structure array with the height of 150 mu m, wherein the array interval is 200 mu m;
(D) Preparing a double-bionic dry tissue adhesive patch: slowly adding the composite tissue adhesive precursor solution prepared in the step (B) into the bionic structure template preheated at 50 ℃ for 10min in the step (C), slightly placing a polydimethylsiloxane tabletting above the bionic structure template, decompressing and removing air bubbles for 60s, irradiating and crosslinking for 40s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch with the thickness of 400 mu m.
Example 5:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
(A) Preparing a hydrogel material of mussel bionic components: dissolving AlgMA powder in PBS (pH 4.6), stirring at 50 deg.C to dissolve to obtain AlgMA solution with concentration of 4%, adding 0.7% EDC and 0.5% NHS,450rpm, activating at room temperature for 45min, adding gallic acid with final concentration of 1.8%, stirring at 37 deg.C, reacting for 15 hr, dialyzing, and freeze drying to obtain final product;
(B) Preparing a precursor solution of the composite tissue adhesive: dissolving the hydrogel material and gelatin powder of the mussel bionic component in the step (A) in PBS according to a certain proportion, respectively preparing gel solutions with the concentration of 7% and 18%, then adding an inorganic hemostatic calcium carbonate, a water-soluble local analgesic procaine and a basf Irgacure2959, and stirring for 2h at 50 ℃;
(C) Processing a male die template of the octopus sucker bionic geometric structure: designing a bionic geometric structure based on a CAD drawing method, and constructing the surface area of a single bionic structure on the surface of the copper alloy by utilizing a precise numerical control milling technology to be 0.05mm 2 A rhombic bionic structure array with the height of 80 mu m, wherein the array interval is 150 mu m;
(D) Preparing a double-bionic dry tissue adhesive patch: slowly adding the composite tissue adhesive precursor solution prepared in the step (B) into the bionic structure template preheated at 50 ℃ for 10min in the step (C), slightly placing a glass pressing sheet above the template, decompressing to remove bubbles for 60s, irradiating and crosslinking for 60s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostatic and analgesic tissue adhesive patch with the thickness of 200 mu m.
Example 6:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
(A) Preparing a hydrogel material of mussel bionic components: dissolving SilMA powder in PBS (pH 4.2), stirring at 50 deg.C to dissolve to obtain 3% SilMA solution, adding 0.3% EDC and 0.1% NHS,350rpm, activating at room temperature for 30min, adding 1% final concentration gallnut aldehyde, stirring at 37 deg.C for 24 hr, dialyzing, and freeze drying;
(B) Preparing a precursor solution of the composite tissue adhesive: dissolving the hydrogel material and gelatin powder of the mussel bionic component in the step (A) in PBS according to a certain proportion, respectively preparing 10% and 10% gel solutions, then adding an inorganic hemostatic calcium carbonate, a water-soluble local analgesic, namely chloroprocaine and phenyl-2, 4, 6-trimethylbenzoyllithium phosphonate, and stirring for 1h at 50 ℃;
(C) Processing a male die template of the octopus sucker bionic geometric structure: based on CAD drawing method, bionic geometric structure is designed, and precise numerical control milling technology is utilized to construct a single bionic structure with the surface area of 0.001mm on the surface of glass 2 A rhombic bionic structure array with the height of 50 mu m, wherein the array interval is 120 mu m;
(D) Preparing a double bionic dry tissue adhesive patch: slowly adding the composite tissue adhesive precursor solution prepared in the step (B) into the bionic structure template preheated at 50 ℃ for 5min in the step (C), slightly placing a polydimethylsiloxane tabletting above the bionic structure template, decompressing and removing air bubbles for 60s, irradiating and crosslinking for 35s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch with the thickness of 120 mu m.
Example 7:
a preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch comprises the following steps:
(A) Preparing a hydrogel material of mussel bionic components: dissolving SilMA powder in PBS (pH 4.5), stirring at 50 deg.C to dissolve to obtain SilMA solution with concentration of 2.5%, adding 0.6% EDC and 0.3% NHS,400rpm, activating at room temperature for 60min, adding gallic acid with final concentration of 0.8%, stirring at 37 deg.C for 18 hr, dialyzing, and freeze drying;
(B) Preparing a precursor solution of the composite tissue adhesive: dissolving the hydrogel material and gelatin powder of the mussel bionic component obtained in the step (A) in PBS according to a certain proportion, respectively preparing 10% and 12% gel solutions, and then adding an inorganic hemostatic calcium carbonate, a water-soluble local analgesic ketorolac tromethamine and phenyl-2, 4, 6-trimethylbenzoyllithium phosphonate for stirring for 2h at 50 ℃;
(C) Octopus sucker bionic tableAnd (3) processing the male die template with the structure: designing a bionic geometric structure based on a CAD drawing method, and constructing the surface area of a single bionic structure on the surface of glass by utilizing a precise numerical control milling technology to be 0.2mm 2 A circular bionic structure array with the height of 180 mu m, wherein the array interval is 250 mu m;
(D) Preparing a double-bionic dry tissue adhesive patch: slowly adding the composite tissue adhesive precursor solution prepared in the step (B) into the bionic structure template preheated at 50 ℃ for 10min in the step (C), slightly placing a polydimethylsiloxane tabletting above the bionic structure template, decompressing and removing air bubbles for 60s, irradiating and crosslinking for 30s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch with the thickness of 250 mu m.
In order to understand the performance of the patch, the double-bionic dry-type rapid hemostasis and analgesia tissue adhesive patch prepared in the embodiment 1-7 is tested, as shown in fig. 7, the double-bionic dry-type rapid hemostasis and analgesia tissue adhesive patch prepared in any one of the embodiment 1-7 is selected to be placed on the surface of different tissues, and the patch cannot fall off or shift, so that the double-bionic dry-type rapid hemostasis and analgesia tissue adhesive patch prepared by the preparation method can be rapidly adhered to moist tissues, has high tissue adhesion strength, and can rapidly close wounds; as shown in fig. 8, the double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch prepared in any one of examples 1 to 7 was placed in an acute bleeding model of rat liver, and the hemostatic time was less than 60 seconds.
In summary, the invention discloses a double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch and a preparation method thereof, wherein the method comprises the following steps: dissolving photo-crosslinkable natural high polymer material powder in a PBS (phosphate buffer solution), stirring until the photo-crosslinkable natural high polymer material powder is dissolved, adding EDC (ethylene diamine tetraacetic acid), NHS (polyethylene glycol) and micromolecules containing a phenol structure, stirring for reaction, dialyzing, and freeze-drying to obtain a mussel bionic component hydrogel material; mixing a hydrogel material of the mussel bionic components and gelatin powder, dissolving the mixture in a PBS solution, activating at room temperature, adding an inorganic hemostatic agent, a water-soluble local analgesic and a photoinitiator, and stirring to obtain a precursor solution of the composite tissue adhesive; designing a bionic geometric structure, and constructing a bionic structure array on the surface of the hard substrate according to the bionic geometric structure to obtain an octopus sucking disc bionic structure male die template; and adding the composite tissue adhesive precursor solution to the octopus sucking disc bionic structure male die template, irradiating for crosslinking, and drying to obtain the double bionic dry type rapid hemostasis and analgesia tissue adhesive patch. The preparation method has the following beneficial effects: 1) The double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch prepared by the invention has the advantages that the sources of the used materials are animals, the biological activity and the safety are high, the controllable biodegradability is realized, the preparation condition is mild, the preparation process is non-toxic and harmless, the prepared dry type tissue adhesive patch has better flexibility and mechanical strength, the tensile strength of the dry type tissue adhesive patch can reach 700 MPa, the tensile strength after swelling can reach 900 kPa, the quality guarantee period is long, and the carrying is convenient; 2) The double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch prepared by the invention has the unique design idea of double bionics, the adhesion strength of the tissue adhesive on the surface of a wet tissue is far higher than that of the existing biological tissue adhesive, the rapid hemostasis effect is good, the blood stopping time in an acute liver bleeding model of a rat is less than 60s, and the analgesia time at a skin wound is more than 5h, so that the patch is the current first dry type tissue adhesive patch which integrates wet tissue adhesion, rapid hemostasis and long-acting analgesia; 3) The double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch prepared by the invention has higher drug and growth factor loading capacity, and can be used for tissue repair while hemostasis and analgesia are realized by controlling the degradability of the tissue adhesive in vivo.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (8)
1. A preparation method of a double-bionic dry type rapid hemostasis and analgesia tissue adhesive patch is characterized by comprising the following steps:
dissolving photo-crosslinkable natural high polymer material powder in PBS (phosphate buffer solution) with pH of 4-5, stirring at 50 ℃ until the photo-crosslinkable natural high polymer material powder is dissolved to obtain 1-5% by mass volume of hydrogel solution, adding 0.1-1% by mass volume of EDC and 0.1-0.6% by mass volume of NHS at a set rotating speed of 300-500rpm, activating at room temperature for 30-60min, adding small molecules containing a phenol structure, stirring at 37 ℃, reacting for 12-24h, dialyzing, and freeze-drying to obtain the hydrogel material of the bionic component of the mussel;
the photocrosslinkable natural high polymer material is a methacrylation natural high polymer material, and the methacrylation natural high polymer material is one of methacryl gelatin, methacryl hyaluronic acid, methacryl sodium alginate, methacryl silk fibroin and methacryl chondroitin sulfate;
the micromolecules containing phenol structures are one or more of dopamine hydrochloride, levodopa, gallic acid, gallaldehyde and trihydroxy benzoyl;
mixing a hydrogel material of the mussel bionic components and gelatin powder, dissolving the mixture in a PBS solution, activating at room temperature, adding an inorganic hemostatic agent, a water-soluble local analgesic and a photoinitiator, and stirring to obtain a precursor solution of the composite tissue adhesive;
designing a bionic geometric structure, and constructing a bionic structure array on the surface of a hard substrate according to the bionic geometric structure to obtain an octopus sucking disc bionic structure male die template;
and adding the composite tissue adhesive precursor solution to the octopus sucking disc bionic structure male die template, irradiating for crosslinking, and drying to obtain the double bionic dry type rapid hemostasis and analgesia tissue adhesive patch.
2. The preparation method of the double bionic dry type rapid hemostatic and analgesic tissue adhesive patch as claimed in claim 1, wherein the inorganic hemostatic agent is one or more of calcium carbonate, calcium chloride, aluminum potassium sulfate and ferric chloride.
3. The method for preparing a double bionic dry type tissue adhesive patch for rapid hemostasis and analgesia as claimed in claim 1, wherein the local analgesic is one or more of lidocaine, bupivacaine, ropivacaine, tetracaine, procaine, chloroprocaine and tromethamine ketolate.
4. The method for preparing a double bionic dry type rapid hemostatic and analgesic tissue adhesive patch according to claim 1, wherein the photoinitiator is lithium phenyl-2, 4, 6-trimethylbenzoylphosphonate or Persff Irgacure2959.
5. The preparation method of the double-bionic dry-type rapid hemostatic and analgesic tissue adhesive patch according to claim 1, wherein the step of designing a bionic geometric structure, constructing a bionic structure array on the surface of a hard substrate according to the bionic geometric structure, and obtaining a male mold template of the bionic structure of the octopus sucker comprises the steps of:
designing a bionic geometric structure of the octopus sucker based on a CAD drawing method;
constructing a bionic structure array on the surface of the hard substrate according to the bionic geometric structure by utilizing an advanced manufacturing technology to obtain an octopus sucking disc bionic structure male die template;
wherein the advanced manufacturing technology comprises one or more of a photocuring 3D printing technology, a fused deposition 3D printing technology, a precise numerical control milling technology and a laser engraving technology.
6. The preparation method of the double bionic dry type rapid hemostatic and analgesic tissue adhesive patch according to claim 5, wherein the hard substrate is one of aluminum alloy, copper alloy, polymethyl methacrylate and glass.
7. The preparation method of the double bionic dry type rapid hemostatic and analgesic tissue adhesive patch according to claim 1, wherein the step of adding the composite tissue adhesive precursor solution to the octopus sucking disc bionic structure male mold template, irradiating for crosslinking, and drying to obtain the double bionic dry type rapid hemostatic and analgesic tissue adhesive patch comprises the steps of:
preheating the male die template of the octopus sucker bionic structure at 50 ℃ for 5-10min;
and adding the composite tissue adhesive precursor solution to a preheated octopus sucking disc bionic structure male die template, placing a pressing sheet above the template, decompressing and removing bubbles, irradiating and crosslinking for 10-60s by using a 405nm blue light lamp, and freeze-drying for 6h to obtain the double-bionic dry-type rapid hemostatic-analgesic tissue adhesive patch.
8. A double bionic dry type rapid hemostatic and analgesic tissue adhesive patch prepared according to any one of claims 1 to 7, wherein the patch comprises an octopus sucking disc bionic structure male template and a hydrogel of mussel bionic components decorated with phenol small molecule structures and arranged on the octopus sucking disc bionic structure male template.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106390185A (en) * | 2016-12-02 | 2017-02-15 | 上海其胜生物制剂有限公司 | Preparation method of biological mimetic tissue adhesive |
| CN112805306A (en) * | 2018-10-04 | 2021-05-14 | 洛桑联邦理工学院 (Epfl) | Crosslinkable polymers, hydrogels and methods for their preparation |
| CN112933284A (en) * | 2021-02-07 | 2021-06-11 | 南京鼓楼医院 | Bionic patch for tissue adhesion and preparation method thereof |
| CN113260301A (en) * | 2018-12-18 | 2021-08-13 | 株式会社爱茉莉太平洋 | Flexible patch capable of being attached to skin and comprising a plurality of through holes and preparation method of flexible patch |
| CN114392382A (en) * | 2022-01-21 | 2022-04-26 | 福州大学 | Double-bionic gel hemostatic composite material for emergency and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3177330A4 (en) * | 2014-08-08 | 2018-01-17 | The Brigham and Women's Hospital, Inc. | Elastic biopolymer and use as a tissue adhesive |
-
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- 2022-06-08 CN CN202210638254.0A patent/CN114949331B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106390185A (en) * | 2016-12-02 | 2017-02-15 | 上海其胜生物制剂有限公司 | Preparation method of biological mimetic tissue adhesive |
| CN112805306A (en) * | 2018-10-04 | 2021-05-14 | 洛桑联邦理工学院 (Epfl) | Crosslinkable polymers, hydrogels and methods for their preparation |
| CN113260301A (en) * | 2018-12-18 | 2021-08-13 | 株式会社爱茉莉太平洋 | Flexible patch capable of being attached to skin and comprising a plurality of through holes and preparation method of flexible patch |
| CN112933284A (en) * | 2021-02-07 | 2021-06-11 | 南京鼓楼医院 | Bionic patch for tissue adhesion and preparation method thereof |
| CN114392382A (en) * | 2022-01-21 | 2022-04-26 | 福州大学 | Double-bionic gel hemostatic composite material for emergency and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| A wet-tolerant adhesive patch inspired by protuberances in suction cups of octopi;Sangyul Baik等;《Nature》;20170615;第546卷;第396-400页 * |
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