阅读说明：本技术 一种功能载体支架的制备方法及应用 (Preparation method and application of functional carrier bracket ) 是由 吴水平 张磊 郑立新 周金生 李珺 于 2021-08-06 设计创作，主要内容包括：本发明公开了一种功能载体支架的制备方法及应用,上述一种功能载体支架,包括依次层叠设置的基体层、第一纤维素层和第一聚四氟乙烯层；所述基体层与所述第一纤维素层边缘以纤维素溶液粘合,且留有开口；所述基体层与所述第一纤维素层间至少有一个腔体。上述单个或者多个腔体的功能载体支架,制备方法中避免了复杂模具的使用,制备方法简单高效,扩展了水凝胶的应用领域。(The invention discloses a preparation method and application of a functional carrier support, wherein the functional carrier support comprises a base layer, a first cellulose layer and a first polytetrafluoroethylene layer which are sequentially stacked; the matrix layer and the edge of the first cellulose layer are bonded by cellulose solution, and an opening is left; at least one cavity is arranged between the substrate layer and the first cellulose layer. The functional carrier bracket with the single or multiple cavities avoids the use of a complex die in the preparation method, the preparation method is simple and efficient, and the application field of the hydrogel is expanded.)

1. A cellulose/polytetrafluoroethylene composite hydrogel film is characterized in that:

comprising a cellulose layer and a polytetrafluoroethylene layer.

2. A functional carrier scaffold prepared from the cellulose/polytetrafluoroethylene composite hydrogel membrane of claim 1, wherein:

the composite material comprises a substrate layer, a first cellulose layer and a first polytetrafluoroethylene layer which are sequentially stacked;

the matrix layer and the edge of the first cellulose layer are bonded by cellulose solution, and an opening is left;

at least one cavity is arranged between the substrate layer and the first cellulose layer.

3. A functional carrier support according to claim 2, wherein:

the base layer comprises a second cellulose layer and a second polytetrafluoroethylene layer which are arranged in a stacked mode, and the second cellulose layer is in contact with the first cellulose layer.

4. A functional carrier support according to claim 3, wherein:

at least one point of the second cellulose layer and the first cellulose layer, which is not at the edge, is coated with a cellulose solution, so that a plurality of communicated cavities are formed between the second cellulose layer and the first cellulose layer.

5. A functional carrier support according to claim 1, wherein:

the substrate layer comprises a cellulose solution.

6. A method of preparing a functional carrier support according to claim 2, wherein: the method comprises the following steps:

the method comprises the steps of sequentially stacking and arranging a first polytetrafluoroethylene layer, a first cellulose layer and a porous material, dropwise adding a cellulose solution into pores of the porous material, standing and gelling, forming a composite film by the first polytetrafluoroethylene layer, the first cellulose layer and the cellulose solution, and stripping the composite film from the porous material, wherein the stripped composite film is provided with at least two cavities which are not contacted with each other.

7. The method of claim 6, wherein: the concentration of the cellulose solution is 0.5 wt% -60 wt%.

8. The method of claim 6, wherein: the standing treatment time is 0.01h-20 h.

9. A carrier for the sustained release of a drug, characterized in that: comprising a functional carrier support according to any one of claims 2 to 5.

10. A cell carrier, comprising: comprising a functional carrier support according to any one of claims 2 to 5.

Technical Field

The invention belongs to the technical field of medical instruments, and particularly relates to a preparation method and application of a functional carrier bracket.

Background

In the field of semipermeable membranes with different base materials, Polytetrafluoroethylene (PTFE) semipermeable membranes have good thermal stability, biocompatibility and high mechanical strength, and are resistant to acid, alkali and organic solvents, so that the PTFE semipermeable membranes are widely applied to the fields of medicine extraction, protein separation, air filtration and the like at present. In addition, in the field of implantable biomedical materials, semipermeable membranes of Polytetrafluoroethylene (PTFE) have been used as artificial blood vessels.

The semi-permeable membrane is packaged into a specific instrument structure to meet specific practical application requirements, which is a necessary link for butting the practical application of the semi-permeable membrane. Such as the attachment of a filter element in a water purifier, the encapsulation of a semipermeable membrane in a filter head. The hydrogel membrane is used for filtering consumables, and the hydrogel membrane packaged into a specific capsule structure can also be used as a carrier for drug slow release and functional cell wrapping. Thermal welding, ultrasonic welding and glue bonding are currently three mainstream film packaging processes, but the method is not suitable for packaging the hydrogel film.

In addition, the preparation of hydrogel macrocapsules with cavity structures usually requires complex molds and the process is complex. Especially, the ultrathin hydrogel macrocapsule is prepared, and the requirement on the precision of the mould is higher.

Disclosure of Invention

The first technical problem to be solved by the invention is as follows:

a functional carrier support is provided.

The second technical problem to be solved by the invention is:

provides a preparation method of the functional carrier bracket.

The third technical problem to be solved by the invention is:

the application of the functional carrier bracket is provided.

The invention also provides a carrier for drug slow release, which comprises the functional carrier bracket.

The invention also provides a cell carrier, which comprises the functional carrier bracket.

A cellulose/polytetrafluoroethylene composite hydrogel film comprises a cellulose layer and a polytetrafluoroethylene layer.

In order to solve the first technical problem, the invention adopts the technical scheme that:

a functional carrier bracket prepared by the cellulose/polytetrafluoroethylene composite hydrogel film comprises:

the base layer, the first cellulose layer and the first polytetrafluoroethylene layer are sequentially stacked;

the edges of the substrate layer and the first cellulose layer are bonded by cellulose solution, and an opening is reserved;

at least one cavity is formed between the substrate layer and the first cellulose layer.

According to an embodiment of the present invention, the method for preparing the cellulose solution includes: adding cotton linters into 7 wt% of NaOH and 12 wt% of urea aqueous solution, shaking for dispersion, precooling the system to below-12 ℃, rapidly stirring and dissolving at room temperature, and centrifuging to remove bubbles to obtain a cellulose solution.

According to one embodiment of the present invention, before the first cellulose layer and the first polytetrafluoroethylene layer are in contact with the base layer, a polytetrafluoroethylene porous membrane is first laid on the surface of a glass sheet, the cellulose solution is poured into the polytetrafluoroethylene membrane surface layer by a tape casting method, and after further scraping and standing treatment, the system is added into a coagulation bath to be coagulated and precipitated, thereby finally obtaining the cellulose/polytetrafluoroethylene composite hydrogel membrane.

According to an embodiment of the present invention, the polytetrafluoroethylene is hydrophilic polytetrafluoroethylene to promote adhesion to the cellulose solution.

According to an embodiment of the present invention, the pore diameter of the Polytetrafluoroethylene (PTFE) porous membrane is 80nm to 8 μm.

According to an embodiment of the present invention, the Polytetrafluoroethylene (PTFE) porous membrane has a thickness of 10 μm to 100 μm.

According to an embodiment of the present invention, the porous Polytetrafluoroethylene (PTFE) membrane is a composite membrane with a support layer, and the support layer is PE, PP, or PET.

According to an embodiment of the present invention, the thickness of the scratch film is 20 μm to 200 μm.

According to an embodiment of the present invention, the standing time is 1min to 1000 min.

According to one embodiment of the invention, the solution used in the coagulation bath is a 10 wt% to 100 wt% aqueous ethanol solution.

According to an embodiment of the present invention, the gelation time is 0.01h to 10 h.

According to one embodiment of the present invention, the base layer includes a second cellulose layer and a second polytetrafluoroethylene layer, which are stacked, and the second cellulose layer is in contact with the first cellulose layer.

According to one embodiment of the invention, at least one point of the non-edges of the second cellulose layer and the first cellulose layer is spot coated with a cellulose solution to form a plurality of communicating cavities between the second cellulose layer and the first cellulose layer.

When the cellulose solution is coated on at least one point of the non-edge of the second cellulose layer and the first cellulose layer, the cellulose solution is adhered to the cellulose layer, so that a plurality of communicated cavities are formed between the second cellulose layer and the first cellulose layer, and the plurality of communicated cavities are structured, so that the expanded composite membrane does not expand and crack.

According to one embodiment of the invention, the matrix layer comprises a cellulose solution.

According to an embodiment of the present invention, the polytetrafluoroethylene membrane contains cellulose in the pores.

According to an embodiment of the present invention, the cellulose has a molecular weight of 10 to 1000 ten thousand

According to an embodiment of the present invention, the pore diameter of the polytetrafluoroethylene/cellulose composite film is in a range of 10 to 100 nm.

In order to solve the second technical problem, the invention adopts the technical scheme that:

a method for preparing the functional carrier bracket comprises the following steps:

and sequentially stacking the first polytetrafluoroethylene layer, the first cellulose layer and the porous material, dripping the cellulose solution into pores of the porous material, standing, and gelling, wherein the first polytetrafluoroethylene layer, the first cellulose layer and the cellulose solution form a composite film, the composite film is peeled from the porous material, and the peeled composite film has at least two cavities which are not contacted with each other.

The cavities which are not in contact with each other or are not communicated with each other can store different medicines or cell solutions, and medicines or cells in other cavities cannot be influenced after any cavity is broken carelessly.

According to one embodiment of the present invention, the concentration of the cellulose solution is 0.5 wt% to 60 wt%.

According to one embodiment of the present invention, the standing treatment time is 0.01h to 20 h.

According to an embodiment of the present invention, the solution for gelation is ethanol.

According to one embodiment of the present invention, the concentration of the above ethanol aqueous solution is 1 wt% to 100 wt%.

According to an embodiment of the present invention, the gelation time is 0.01h to 20 h.

The hydrogel is an aqueous material, the pore structure of which can be regulated by the cross-linking structure and density, and has the function of a semipermeable membrane, so that the hydrogel is widely used as a carrier of cells or drugs. However, conventional hydrogel ultrathin films (e.g., those having a thickness of 50 μm or less) have poor strength and are easily curled, and thus are difficult to be effectively applied in practice. The invention takes a PTFE semipermeable membrane as a base material, and the pore of the PTFE original membrane is regulated and controlled by compounding hydrogel on the surface layer. The thickness of the PTFE film can be randomly regulated and controlled between 10 mu m and 100 mu m, and the thickness of the composite film can be regulated and controlled at 15 mu m or 100 mu m.

The surface layer of the PTFE membrane only has inert groups and no grafting sites. After the surface layer is introduced with cellulose, hydroxyl of the surface layer is an active functional group and can be used as a grafting modification site. The hydroxyl can react with active components such as chlorohydrocarbon, epoxy and the like, for example, 2-bromine isobutyryl bromide is grafted on the hydroxyl by an ATRP technology, and components such as zwitterion, amino acid and the like can be further grafted.

In still another aspect of the present invention, there is also provided a carrier for sustained release of a drug, comprising a functional carrier scaffold as described above.

In still another aspect of the present invention, there is also provided a cell carrier comprising a functional carrier scaffold as described above.

One of the above technical solutions has at least the following advantages or beneficial effects:

(1) the polytetrafluoroethylene and the cellulose both have good biocompatibility, and the sources are wide, cheap and easily available. The introduction of cellulose into the pores of the polytetrafluoroethylene membrane can introduce active grafting sites for subsequent surface layer grafting modification.

(2) When a plurality of communicated cavities are formed in the functional carrier support, the plurality of communicated cavity structures enhance the stability of the functional carrier support, and when a medicinal solution or a cell solution is filled in the functional carrier support, the middle part of the expanded functional carrier support cannot be cracked.

(3) When a plurality of cavities which are not communicated and are not contacted are formed in the functional carrier bracket, different medicines or cell solutions can be stored in each cavity, and medicines or cells in other cavities cannot be influenced after any cavity is broken carelessly.

(4) The functional carrier bracket with the single or multiple cavities avoids the use of a complex die in the preparation method, the preparation method is simple and efficient, and the application field of the hydrogel is expanded.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

FIG. 1 is a diagram of a functional carrier support.

FIG. 2 is a mechanical property test chart of the cellulose/polytetrafluoroethylene hydrogel composite membrane.

FIG. 3 is a graph showing permeability test of a cellulose/Polytetrafluoroethylene (PTFE) hydrogel composite membrane.

Detailed Description

Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout.

The embodiments described below with reference to the accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.

In the description of the present invention, if there are first, second, third, etc. described only for the purpose of distinguishing technical features, it is not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.

In the description of the present invention, it should be understood that the orientation or positional relationship referred to in the description of the orientation, such as the upper, lower, left, right, etc., is based on the orientation or positional relationship shown in the drawings, and is only for convenience of description and simplicity of description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention.

In the description of the present invention, it should be noted that unless otherwise explicitly defined, terms such as arrangement, installation, connection and the like should be broadly understood, and those skilled in the art can reasonably determine the specific meanings of the terms in the present invention in combination with the detailed contents of the technical solutions.

In order to explain the technical content, the objects and the effects of the present invention in detail, the following description will be given with reference to the embodiments.

Example 1

1) Preparing 40g of mixed solution of 7 wt% NaOH and 12 wt% urea, adding 10g of cotton linter cellulose with the molecular weight of 100 ten thousand Da into the mixed solution, and oscillating and dispersing. Then, the system is frozen and stored for 10 hours at the temperature of minus 20 ℃, is rapidly stirred and dissolved to be in a transparent and clear state at room temperature, and is centrifuged to remove bubbles, so that a 20 wt% cellulose solution is obtained;

2) a hydrophilic Polytetrafluoroethylene (PTFE) porous membrane having a thickness of 40 μm and a pore diameter of 220nm was laid on the surface of a glass plate, the cellulose solution was poured onto the surface layer of the Polytetrafluoroethylene (PTFE) membrane, and the membrane was scraped with a wire bar coater having a thickness of 54.9. mu.m. And then standing for 5 hours, adding the system into a coagulating bath of 50 wt% ethanol water solution for gelling treatment for 3 hours, and finally obtaining the cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel membrane.

Example 2

1) Preparing 30g of 7 wt% NaOH/12 wt% urea mixed solution, adding 10g of cotton linter cellulose with the molecular weight of 200 ten thousand Da into the mixed solution, and fully shaking and dispersing. Then, the system is frozen and stored for 10 hours at the temperature of minus 20 ℃, rapidly stirred and dissolved at room temperature to be in a transparent and clear state, and air bubbles are removed by centrifugation to obtain a 15 wt% cellulose solution;

2) the cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel membrane (cellulose membrane side up) prepared according to the above method was laid on a glass plate, and a 10 wt% cellulose solution was slowly extruded at a rate of 1ml/min onto a specific site on the surface of the cellulose membrane using a micro peristaltic pump. Then another cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel film (cellulose side down) is laid on the surface of the composite film and is left for 1 h. And finally placing the composite membrane in 20 wt% of ethanol water solution for gelling for 2h, and washing the composite membrane for multiple times by using a large amount of deionized water to obtain the cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel large support with a cavity structure. The central hydrogel cavity may be used for drug or cell encapsulation.

Example 3

1) Preparing 45g of 7 wt% NaOH/12 wt% urea mixed solution, adding 5g of cotton linter cellulose with the molecular weight of 50 ten thousand Da into the mixed solution, fully vibrating and dispersing, then freezing and storing the system at-20 ℃ for 10h, rapidly stirring and dissolving at room temperature to a transparent and clear state, and centrifuging to remove bubbles to obtain a 10 wt% cellulose solution;

2) pouring a cellulose solution into a mold, then spreading a Polytetrafluoroethylene (PTFE)/cellulose composite film (with the cellulose side facing downwards) prepared according to the step of example 1 on the surface layer of the mold containing the cellulose solution, flattening the film with a glass rod, standing the film for 2 hours, then carrying out gelling treatment in a 30 wt% ethanol coagulating bath for 2 hours, washing the film with a large amount of deionized water for multiple times to finally obtain a multi-cavity structure cellulose composite stent, and covering the surface layer of the multi-cavity structure cellulose composite stent with a layer of the Polytetrafluoroethylene (PTFE)/cellulose composite film, thereby forming the closed multi-cavity structure cellulose composite stent.

FIG. 2 is a mechanical property test chart of the cellulose/polytetrafluoroethylene hydrogel composite membrane.

As can be seen from fig. 2, the strength and flexibility (elongation) of the composite membrane are improved compared to the PTFE membrane and the cellulose membrane of a single component.

FIG. 3 is a graph showing permeability test of a cellulose/Polytetrafluoroethylene (PTFE) hydrogel composite membrane.

The permeation efficiency chart of the composite membrane shows that the composite membrane can efficiently intercept macromolecules such as 150kDa IgG and the like, and the permeation rate can be controlled within 5 percent; meanwhile, the osmotic filtration of FITC-dextran small molecules with 10kDa is not influenced, which shows that the composite membrane is a semipermeable membrane which can be used for aiming at substances with specific molecular weight.

The above description is only an example of the present invention and is not intended to limit the scope of the present invention, and all equivalent modifications made by the present invention as described in the specification of the present invention or directly or indirectly applied to the related technical fields are included in the scope of the present invention.