CN114939188B

CN114939188B - Skull base repair film after nasal butterfly access operation and preparation method thereof

Info

Publication number: CN114939188B
Application number: CN202210471278.1A
Authority: CN
Inventors: 崔云; 宋天喜; 何志敏; 胡艳丽; 朱金亮; 仇志烨; 吴晶晶; 胡刚
Original assignee: Shandong Aojing Biotechnology Co ltd; Aojing Medical Technology Co ltd
Current assignee: Shandong Aojing Biotechnology Co ltd; Aojing Medical Technology Co ltd
Priority date: 2022-04-28
Filing date: 2022-04-28
Publication date: 2023-10-13
Anticipated expiration: 2042-04-28
Also published as: CN114939188A

Abstract

The invention relates to the technical field of repair membranes, in particular to a skull base repair membrane after a nasal butterfly access operation and a preparation method thereof. A method for preparing a skull base repair membrane after a transnasal butterfly access operation, comprising the following steps: preparing a compact layer by adopting a macromolecule or biological protein solution; uniformly mixing the macromolecule or biological protein solution with bone powder to obtain a mixture; preparing a bone layer on the surface of the compact layer by adopting the mixture; and preparing a sealing layer on one surface of the osteogenesis layer far away from the compact layer by adopting the macromolecule or biological protein solution to obtain the skull base repair film. The embodiment of the invention provides a skull base repair membrane after a transnasal butterfly access operation and a preparation method thereof, which can effectively repair the skull base after the transnasal butterfly access operation.

Description

Skull base repair film after nasal butterfly access operation and preparation method thereof

Technical Field

The invention relates to the technical field of repair membranes, in particular to a skull base repair membrane after a nasal butterfly access operation and a preparation method thereof.

Background

With the development of microscopy and endoscopic techniques, the transnasal butterfly approach can be used for the treatment of anterior skull base trauma, tumors, saddle space occupation, and three ventricle, mid-upper slope lesions. Neurosurgeons typically choose to open the sphenoid sinus, and even part of the ethmoid sinus, and abrade the bone at the bottom of the saddle to expose the diseased tissue that needs to be resected. The bone of the saddle floor acts as an important load-bearing structure from which, once opened, the brain contents and cerebrospinal fluid (cerebrospinal fluid, CSF) are easily leaked into the nasal cavity due to gravity. The cranial cavity is not a closed space at this time, but is communicated with the external environment, and the repair is needed in time during operation; otherwise, complications such as CSF leakage, intracranial qi accumulation, intracranial infection, cerebral bulging and the like are easily caused, and the serious risk and even death are caused to the operation.

In the related art, the method for closing the skull base defect comprises autologous fat transplantation, dural suture, fascia transplantation and repairing by combining nasal septum vessel skin flaps with a hard material support. However, adipose tissue as a repair material may affect the reliability of repair due to liquefaction of fat; the dura mater is used as a repairing material, has poor repairing capability and is easy to cause the CSF to leak again after operation; fascia as a repair material requires long post-operation bedridden time of the patient and is prone to long-term bedridden complications; the combined use of a stiff material support for the nasal septum vessel flap as a repair material may cause infection or prevent epithelialization, and if the tumor recurs again, it may become difficult to re-enter the stiff material support. That is, none of the above-described related art is effective in repairing the skull base after a transnasal butterfly access procedure.

Therefore, in order to overcome the above disadvantages, there is an urgent need for a skull base repair film after a transnasal butterfly access operation and a preparation method thereof.

Disclosure of Invention

The embodiment of the invention provides a skull base repair membrane after a transnasal butterfly access operation and a preparation method thereof, which can effectively repair the skull base after the transnasal butterfly access operation.

In a first aspect, an embodiment of the present invention provides a method for preparing a skull base repair film after a nasal butterfly access operation, including:

preparing a compact layer by adopting a macromolecule or biological protein solution;

uniformly mixing the macromolecule or biological protein solution with bone powder to obtain a mixture;

preparing a bone layer on the surface of the compact layer by adopting the mixture;

and preparing a sealing layer on one surface of the osteogenesis layer far away from the compact layer by adopting the macromolecule or biological protein solution to obtain the skull base repair film.

In one possible design, the preparation of the dense layer using a polymer or bioprotein solution includes:

and drying the macromolecule or biological protein solution to obtain the compact layer.

In one possible design, the preparing the bone layer on the surface of the dense layer using the mixture includes:

coating the mixture on the surface of the compact layer;

and carrying out freeze-drying treatment on the mixture coated on the surface of the compact layer to obtain the osteogenic layer.

In one possible design, after the step of preparing the bone formation layer on the surface of the dense layer with the mixture and before the step of preparing the sealing layer on the side of the bone formation layer away from the dense layer with the polymer or bioprotein solution, the method further comprises:

and carrying out crosslinking treatment on the compact layer and the osteogenic layer.

In one possible design, the preparing a sealing layer on a side of the osteogenic layer remote from the dense layer using the polymer or bioprotein solution includes:

coating the macromolecule or biological protein solution on one surface of the osteogenic layer far away from the compact layer;

and carrying out freeze-drying treatment on the macromolecule or biological protein solution coated on the osteogenic layer to obtain a sealing layer.

In one possible design, the mass ratio of solute in the polymer or bioprotein solution to the bone meal in the mixture is (0.5-1): 99.

In one possible design, the dense layer has a thickness of 0.1 to 0.2mm;

and/or the number of the groups of groups,

the thickness of the osteogenic layer is 0.2-0.3 mm;

and/or the number of the groups of groups,

the thickness of the sealing layer is 0.2-5 mm.

In one possible design, the polymer or bioprotein solution comprises at least one of collagen gel, silk fibroin, polycaprolactone, polyurethane, silicone rubber, polyester fiber, polyvinylpyrrolidone, polyetheretherketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene, and gelatin.

In one possible design, the bone powder comprises at least one of mineralized collagen particles, sintered hydroxyapatite, and beta-tricalcium phosphate.

In a second aspect, an embodiment of the present invention provides a skull base repair membrane after a nasal butterfly access, which is prepared by using the preparation method according to any one of the first aspects, wherein the dense layer is a side facing the outside of the brain, the sealing layer is a side facing the inside of the brain, and the skull base repair membrane is used for repairing a skull base defect after a nasal butterfly access.

Compared with the prior art, the invention has at least the following beneficial effects:

in some embodiments of the invention, a polymer or biological protein solution is used to prepare a compact layer, and the compact layer has high strength and a protection function; the bone powder is prepared by uniformly mixing a polymer or biological protein solution with bone powder, bonding the bone powder together by the polymer or biological protein solution to obtain a mixture with certain plasticity, coating the mixture on the surface of a compact layer to obtain a bone formation layer with certain plasticity, wherein the bone formation layer with plasticity can be subjected to micro deformation to adapt to external force when the external force is applied, so that the bone formation layer can adapt to irregular skull base breakage, in addition, the bone formation layer formed by the bone powder has supportability, and simultaneously, bone regeneration can be promoted by the bone powder, and the micropore structure of the bone powder can provide space for the formation of new bone tissues, so that the bone formation layer and the bone tissues can be better combined; the sealing layer is prepared on the surface of the osteogenesis layer far away from the compact layer by adopting a high polymer or biological protein solution, the sealing layer has the property of absorbing water and swelling, once cerebrospinal fluid seeps out, the sealing layer swells after absorbing the cerebrospinal fluid, and the swelled sealing layer has the water purification pressure, so that the damage of the skull base can be sealed, and the leakage of the cerebrospinal fluid is prevented. Therefore, the skull base repair membrane composed of the compact layer, the osteogenesis layer and the sealing layer has the functions of protecting, supporting and promoting bone tissue growth and sealing cerebrospinal fluid, and can effectively repair skull base defects after the transnasal butterfly access operation.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a flow chart of a method for preparing a cranium base repair membrane after a transnasal butterfly access procedure according to an embodiment of the present invention;

FIG. 2 is a flow chart of another method for preparing a post-nasal butterfly access cranium base repair membrane according to an embodiment of the invention;

FIG. 3 is a cross-sectional view of a post-percutaneous repair membrane for a transnasal butterfly approach according to an embodiment of the invention;

in the figure:

1-a dense layer;

2-an osteogenic layer;

3-a sealing layer;

10-mould.

Detailed Description

For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of 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, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments, and all other embodiments obtained by those skilled in the art without making any inventive effort based on the embodiments of the present invention are within the scope of protection of the present invention.

In the description of embodiments of the present invention, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying any relative importance unless explicitly specified or limited otherwise; the term "plurality" means two or more, unless specified or indicated otherwise; the terms "connected," "secured," and the like are to be construed broadly, and may be, for example, fixedly connected, detachably connected, integrally connected, or electrically connected; can be directly connected or indirectly connected through an intermediate medium. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art according to the specific circumstances.

In the description of the present specification, it should be understood that the terms "upper", "lower", and the like used in the embodiments of the present invention are described in terms of the angles shown in the drawings, and should not be construed as limiting the embodiments of the present invention. In the context of this document, it will also be understood that when an element is referred to as being "on" or "under" another element, it can be directly on the other element or be indirectly on the other element through intervening elements.

As shown in fig. 1, the embodiment of the invention provides a preparation method of a skull base repair membrane after a nasal butterfly access operation, which comprises the following steps:

step 100, preparing a compact layer by adopting a macromolecule or biological protein solution;

102, uniformly mixing the macromolecule or biological protein solution with bone powder to obtain a mixture;

104, preparing a bone layer on the surface of the compact layer by adopting the mixture;

and 106, preparing a sealing layer on the surface of the osteogenesis layer far away from the compact layer by adopting a high polymer or biological protein solution to obtain the skull base repair film.

The solute mass fraction of the polymer or biological protein solution is 1-1.5%.

The effect of the sealing layer is similar to that of fat, but compared with the fat, the sealing layer cannot slip, cannot liquefy, and is more stable and durable.

In some embodiments of the present invention, the above-mentioned dense layer, bone formation layer and sealing layer may be prepared by using a mold, for example, a polymer or bioprotein solution may be coated on a mold bottom layer, a mold upper layer is covered and dried to obtain a uniformly spread dense layer, the dense layer is placed on the mold bottom layer after the dense layer is obtained, the mixture is coated on the dense layer, a mold upper layer is covered and dried to obtain a bone formation layer which is bonded with the dense layer and uniformly spread, and the dense layer and bone formation are placed on the mold bottom layer, wherein the dense layer is attached to the mold bottom layer, the polymer or bioprotein solution is coated on the bone formation layer, and a mold upper layer is covered and dried to obtain a sealing layer which is bonded with the bone formation layer and uniformly spread.

The drying treatment may be a drying treatment or a freeze-drying treatment.

In some embodiments of the invention, the distance between the bottom mold layer and the upper mold layer can be adjusted, and dense, osteogenic and sealing layers of different thicknesses can be prepared by controlling the distance between the bottom mold layer and the upper mold layer.

In order to better fit the skull base damage after the transnasal butterfly access operation, a mold with a curved surface inside can be selected to prepare a curved compact layer, an osteogenic layer and a sealing layer.

In some embodiments of the invention, the material from which the mold is made includes polytetrafluoroethylene and metal.

In some embodiments of the present invention, when using the skull base repair film provided by the present invention to repair a skull base damage, a bio-adhesive may be coated on the edge of the skull base repair film to tightly bond the skull base repair film and the skull base.

According to some preferred embodiments, the dense layer is prepared using a polymer or bioprotein solution comprising:

drying the macromolecule or biological protein solution to obtain a compact layer.

In some embodiments of the invention, the polymer or biological protein solution is subjected to drying treatment, so that the prepared compact layer is more compact and has stronger mechanical strength, wherein the drying treatment temperature is 40 ℃, and the drying time is 12-24 hours.

According to some preferred embodiments, the mixture is used to prepare a bone layer on the surface of the dense layer, comprising:

coating the mixture on the surface of the compact layer;

and (3) carrying out freeze-drying treatment on the mixture coated on the surface of the compact layer to obtain the osteogenic layer.

In some embodiments of the invention, the lyophilization process can fix the shape of the osteogenic layer, increase the hardness, increase the pore size of the microporous structure in the osteogenic layer, increase the supporting strength of the osteogenic layer, and further, since the dense layer and the osteogenic layer both contain high molecular or biological proteins, the lyophilization process can bond the dense layer and the osteogenic layer together.

In some embodiments of the invention, the lyophilization process includes a pre-freezing stage, a first sublimation stage, a second sublimation stage, and a cooling stage, the process conditions for each stage being as follows:

pre-freezing: the target temperature is-12 to-8 ℃, the speed is 3-4.0 ℃/min, and the constant temperature duration is 280-320 min;

a first sublimation stage: vacuumizing, aerating at 90-110 Pa, wherein the target temperature is-4 to-2 ℃, the speed is 0.6-0.8 ℃/min, and the constant temperature duration is 1300-1340 min;

in the second sublimation stage, vacuumizing, and aerating at 90-110 Pa, wherein the second sublimation stage comprises five temperature rising steps of respectively:

-1 ℃, the speed is 0.2-0.3 ℃/min, and the constant temperature duration is 110-130 min;

8-12 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;

the temperature is 18-22 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;

28-32 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;

38-42 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is as follows: performing end point judgment every 10 minutes until the end point judgment is qualified; judging the end point to be less than or equal to 0.9Pa/10min;

and (3) a cooling stage: cooling to room temperature at a speed of 1.4-1.6 ℃/min.

According to some preferred embodiments, after preparing the bone layer with the mixture on the surface of the dense layer and before preparing the sealing layer with the polymer or bioprotein solution on the side of the bone layer remote from the dense layer, further comprising:

and (3) carrying out crosslinking treatment on the compact layer and the osteogenic layer.

In some embodiments of the invention, the cross-linking treatment can prevent the dense layer and the osteogenic layer from swelling when contacting water, prevent delamination caused by swelling, increase the stability of the skull base repair film and increase the degradation period of the skull base repair film.

In some embodiments of the invention, the process of crosslinking treatment comprises:

a. preparing a cross-linking agent solution: the edible alcohol with a certain volume is measured by a measuring cylinder and is transferred into a reaction kettle, glutaraldehyde solution with a certain volume (the mass fraction of glutaraldehyde is 50%) is transferred by a liquid transferring gun, and the volume ratio of the edible alcohol to the glutaraldehyde solution is 100: preparing glutaraldehyde alcohol solution in a proportion of 0.05;

b. the material is soaked in the crosslinking liquid, the stirring speed of the reaction kettle is 20-30r/min, and the uppermost material can rotate along with stirring and is crosslinked for 48h. (Note: when crosslinking, after the material adsorbed the crosslinking agent and sunk, if the material is below the stirring paddle, the stirring paddle is not in contact with the material, the stirring speed is reduced, instead 10r/min. If the stirring paddle is in contact with the material, the stirring is turned off).

c. Washing process

(1) Taking the crosslinked material out of the crosslinking agent solution;

(2) The centrifuge loads the filter bag and centrifuges once (5 seconds); the rotational speed of the centrifugal machine defaults to 3000r/min;

(3) Soaking with 3% hydrogen peroxide solution for 42+ -1 h at a ratio of 1:80, i.e. 3% hydrogen peroxide solution volume (ml) =product mass (g) ×80, the product being completely immersed in hydrogen peroxide solution.

(4) Performing ultrasonic treatment on the purified water for 30min, and centrifuging once (5 s) after ultrasonic treatment; repeating for 2 times;

(5) The edible alcohol is treated by ultrasonic for 5min, and the volume of the edible alcohol is based on the principle of immersing the product. After the ultrasonic treatment is finished, the centrifugal operation is carried out once (5 seconds);

d. vacuum drying

And (3) loading the centrifuged material into a vacuum drying oven for vacuum drying, wherein the vacuum degree is not higher than-0.08 Mpa, the temperature is set to be 50 ℃, and the drying is carried out for at least 24 hours.

According to some preferred embodiments, the sealing layer is prepared with a polymer or bioprotein solution on the side of the osteogenic layer remote from the dense layer, comprising:

coating a macromolecule or biological protein solution on one surface of the osteogenic layer far away from the compact layer;

and carrying out freeze-drying treatment on the polymer or biological protein solution coated on the osteogenic layer to obtain the sealing layer.

In some embodiments of the invention, the lyophilization process may also bond the dense layer, the osteogenic layer, and the sealing layer together. The lyophilization process is the same as above and will not be described in detail herein.

The compact layer and the sealing layer are both made of polymer or biological protein solution, and the difference is that the compact layer is made by baking treatment, the obtained compact layer is compact sheet-shaped, the sealing layer is made by freeze-drying treatment, and the obtained sealing layer is loose sponge-shaped.

According to some preferred embodiments, the mass ratio of solute to bone meal in the polymer or bioprotein solution in the mixture is (0.5-1): 99 (e.g., may be 0.5:99, 0.6:99, 0.7:99, 0.8:99, 0.9:99, or 1:99).

In some embodiments of the invention, the mass ratio of the solute of the polymer or the biological protein solution to the bone meal is (0.5-1): 99, wherein the polymer or the biological protein solution plays a role in binding, can bind the bone meal together to form a mixture with plasticity and viscosity, and if the mass ratio of the solute of the polymer or the biological protein solution to the bone meal is less than 0.5:99, the bone meal cannot be all bound together; if the mass ratio of the solute of the polymer or the biological protein solution to the bone powder is more than 1:99, the aperture and the porosity of the mixture after freeze-drying are higher, the sponginess is stronger, and the supporting effect is weakened.

According to some preferred embodiments, the thickness of the dense layer is 0.1 to 0.2mm (e.g., may be 0.1mm, 0.11m, 0.12m, 0.13m, 0.14mm, 0.15mm, 0.16mm, 0.17mm, 0.18mm, 0.19mm, or 0.2 mm);

and/or the number of the groups of groups,

the thickness of the osteogenic layer is 0.2 to 0.3mm (for example, 0.2mm, 0.21mm, 0.22mm, 0.23mm, 0.24mm, 0.25mm, 0.26mm, 0.27mm, 0.28mm, 0.29mm or 3 mm);

and/or the number of the groups of groups,

the thickness of the sealing layer is 0.2 to 5mm (for example, may be 0.2mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm or 5 mm).

In some embodiments of the invention, the thickness of the dense layer, the osteogenic layer and the sealing layer are thinner, so that the requirement of repairing the skull base damage can be met, the sealing layer is thicker than other layers, and the thicker sealing layer can further increase the sealing effect of the swelled sealing layer.

According to some preferred embodiments, the polymer or bioprotein solution comprises at least one of collagen gel, silk fibroin, polycaprolactone, polyurethane, silicone rubber, polyester fiber, polyvinylpyrrolidone, polyetheretherketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene, and gelatin.

In some embodiments of the present invention, collagen gel, silk fibroin, polycaprolactone, polyurethane, silicone rubber, polyester fiber, polyvinylpyrrolidone, polyetheretherketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene, and gelatin are well-established in application technology, and have good biocompatibility. In some embodiments of the invention, a method of preparing a collagen sol comprises:

(1) Removing superfluous fascia, fat, muscle and the like on the beef achilles tendon, washing with tap water, and orderly arranging in a freezing box for freezing at-20 ℃ for at least 12 hours;

(2) Cutting frozen Achilles tendon into slices of about 1mm, and placing into a filter screen for turning and washing until the liquid is clear;

(3) Enzymolysis: carrying out enzymolysis on the cleaned beef achilles tendon slices, and fully stirring, wherein the enzymolysis time is not less than 72 hours; wherein the mass ratio of the enzymolysis liquid to the bovine Achilles tendon is 130:1, the volume ratio of purified water to acetic acid in the enzymolysis liquid is 25:1, the mass ratio of the purified water to the pepsin is 15:1.

(4) Salting out: centrifuging the solution after enzymolysis, taking supernatant, adding the supernatant into sodium chloride solution, separating out white flocculent collagen, filtering and cleaning, and draining water.

(5) And (3) dialysis: filling the salted-out material into a dialysis bag, wherein the filling volume is about 1/3 of that of the dialysis bag; placing the dialysis bag in 0.057mol/L acetic acid solution for 6 days, and changing the dialysis solution every 3 days at 10-20deg.C; then placing the dialysis bag in 0.00057mol/L acetic acid solution for dialysis for 5 days, wherein the dialysis temperature is 10-20 ℃, and the dialysate is changed every 1 day; dialyzing in 0.0000057mol/L acetic acid solution from day 12 to pH 5.0-5.5, and dialyzing at 10-20deg.C, and changing dialysate once daily as required.

(6) The collagen gel was removed and tested for solids content.

In some embodiments of the invention, a method of preparing a silk fibroin comprises:

placing mulberry silk into 0.02mol/L Na at 100deg.C ₂ CO ₃ Boiling in solution twice for 30min each time, washing with tap water and distilled water for several times to thoroughly remove sericin, and air drying for use. Dissolving degummed silk in LiBr solution of 9.3mol/L, dissolving at 60deg.C for 4h, dialyzing for 3d (molecular weight cut-off is 12000-14000) to obtain silk solution with concentration of 8%, centrifuging at 12000rpm for 15min, concentrating low concentration PEG solution for a certain time to obtain high concentration silk solution, centrifuging at 12000rpm for 15min, centrifuging, and measuring concentration by dry constant weight method. Placing in a refrigerator at 4 ℃ for standby.

According to some preferred embodiments, the bone powder comprises at least one of mineralized collagen particles, sintered hydroxyapatite, and beta-tricalcium phosphate.

In some embodiments of the invention, mineralized collagen particles, sintered hydroxyapatite, and beta-tricalcium phosphate are well-established in application techniques, are biocompatible, have a microporous structure, and are capable of promoting bone tissue growth.

In some embodiments of the invention, a method of preparing mineralized collagen particles comprises:

step 1, dissolving collagen in any one of hydrochloric acid, nitric acid or acetic acid to prepare an acid solution of the collagen, wherein the concentration of the collagen is 0.01-0.2 g/ml;

step 2, dropwise adding a calcium salt solution into the acid solution of the collagen, wherein the adding amount of calcium ions is 0.1-2 mol of calcium ions added into each gram of collagen;

step 3, dropwise adding a phosphoric acid solution into the solution obtained in the step 2, wherein the molar ratio of the adding amount of phosphate ions to the adding amount of calcium ions in the step 2 is Ca/P=1/1-2/1;

step 4, dropwise adding a NaOH solution into the solution obtained in the step 3 to form a mixed solution, and regulating the pH value to be 6-8;

step 5, standing the mixed solution obtained in the step 4 for 4-12 hours, centrifuging at a speed of 3000-6000 r/min to obtain precipitate, and drying at 50-70 ℃ for 24-72 hours by air blast to obtain mineralized collagen particles;

step 6, a crushing procedure, namely placing mineralized collagen particles in a small crusher, and crushing for 0.5s to form fine particles;

step 7, screening the crushed materials by using a vibrating screen or a stainless steel screen, wherein the mesh number of the upper layer screen is about 18 meshes (the particle size of corresponding material particles is less than 1000 mu m), and the mesh number of the lower layer screen is about 60 meshes for interception (the particle size of corresponding material particles is more than 250 mu m); the particles trapped by the 60 mesh sieve are collected, and the material trapped by the 18 mesh sieve is continued to be crushed, and the steps are repeated.

As shown in fig. 2, the embodiment of the invention further provides another preparation method of the skull base repair membrane after the transnasal butterfly access operation, which comprises the following steps:

step 200, drying the macromolecule or biological protein solution to obtain a compact layer;

step 202, uniformly mixing a macromolecule or biological protein solution and bone meal to obtain a mixture;

step 204, coating the mixture on the surface of the compact layer;

step 206, carrying out freeze-drying treatment on the mixture coated on the surface of the compact layer to obtain an osteogenic layer;

step 208, performing cross-linking treatment on the compact layer and the osteogenic layer;

step 210, coating a macromolecule or biological protein solution on one surface of the osteogenic layer far away from the compact layer;

step 212, lyophilizing the polymer or biological protein solution coated on the osteogenic layer to obtain a sealing layer.

As shown in fig. 3, the embodiment of the invention further provides a skull base repair film after the transnasal butterfly access, which is prepared by adopting the preparation method of any one of the above steps, wherein the compact layer 1 is the side facing the outside of the brain, the sealing layer 3 is the side facing the inside of the brain, and the skull base repair film is used for repairing the skull base defect after the transnasal butterfly access.

It should be noted that, the skull base repair membrane after the transnasal butterfly access operation is prepared by the preparation method of the skull base repair membrane after the transnasal butterfly access operation, and the two are based on the same inventive concept, so that the same technical effects can be obtained.

In order to more clearly illustrate the technical scheme and advantages of the invention, the following describes a skull base repair film after a transnasal butterfly access operation and a preparation method thereof in detail through a plurality of embodiments.

Example 1

Drying the collagen gel to obtain a compact layer;

uniformly mixing collagen gel and sintered hydroxyapatite to obtain a mixture, wherein the mass ratio of solute in the collagen gel to the sintered hydroxyapatite is 0.5:99, a step of;

coating the mixture on the surface of the compact layer;

lyophilizing the mixture coated on the surface of the compact layer to obtain an osteogenic layer;

crosslinking the compact layer and the osteogenic layer;

coating collagen gel on one surface of the osteogenic layer far away from the compact layer;

carrying out freeze-drying treatment on the collagen gel coated on the osteogenic layer to obtain a sealing layer;

wherein the thickness of the compact layer is 0.1mm, the thickness of the osteogenic layer is 0.2mm, and the thickness of the sealing layer is 0.2mm.

Example 2

Drying the silk fibroin solution to obtain a compact layer;

uniformly mixing a silk fibroin solution and mineralized collagen particles to obtain a mixture, wherein the mass ratio of solute in the silk fibroin solution to the mineralized collagen particles is 1:99, a step of;

coating the mixture on the surface of the compact layer;

crosslinking the compact layer and the osteogenic layer;

coating silk fibroin solution on one surface of the osteogenic layer far away from the compact layer;

carrying out freeze-drying treatment on the silk fibroin solution coated on the osteogenic layer to obtain a sealing layer;

wherein, the thickness of the compact layer is 0.2mm, the thickness of the osteogenic layer is 0.3mm, and the thickness of the sealing layer is 5mm.

Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a skull base repair membrane after a transnasal butterfly access operation, which is characterized by comprising the following steps:

preparing a sealing layer on one surface of the osteogenic layer far away from the compact layer by adopting the macromolecule or biological protein solution to obtain a skull base repair film;

in the mixture, the mass ratio of the solute in the polymer or biological protein solution to the bone meal is (0.5-1): 99, so that the bone formation layer has plasticity and supportability;

the thickness of the compact layer is 0.1-0.2 mm;

the thickness of the osteogenic layer is 0.2-0.3 mm;

the thickness of the sealing layer is 0.2-5 mm;

the polymer or biological protein solution comprises at least one of collagen gel, silk fibroin, polycaprolactone, polyurethane, silicone rubber, polyester fiber, polyvinylpyrrolidone, polyether ether ketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene and gelatin.

2. The method of claim 1, wherein the preparing a dense layer using a polymer or bioprotein solution comprises:

3. The method of claim 1, wherein the preparing a bone layer on the surface of the dense layer using the mixture comprises:

coating the mixture on the surface of the compact layer;

4. The method of claim 1, further comprising, after said preparing a bone layer with the mixture on the surface of said dense layer and before said preparing a sealing layer with said polymer or bioprotein solution on the side of said bone layer remote from said dense layer:

5. The method of claim 1, wherein the preparing a sealing layer on a side of the osteogenic layer away from the dense layer using the polymer or bioprotein solution comprises:

6. The method of preparing according to claim 1, wherein the bone powder comprises at least one of mineralized collagen particles, sintered hydroxyapatite, and β -tricalcium phosphate.

7. A post-nasal butterfly access skull base repair membrane, characterized in that the membrane is prepared by the preparation method of any one of claims 1-6, wherein the dense layer is the side facing the outside of the brain, the sealing layer is the side facing the inside of the brain, and the skull base repair membrane is used for repairing the post-nasal butterfly access skull base defect.