CN113769102B - Preparation method and application of functional carrier bracket - Google Patents

Preparation method and application of functional carrier bracket Download PDF

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Publication number
CN113769102B
CN113769102B CN202110903040.7A CN202110903040A CN113769102B CN 113769102 B CN113769102 B CN 113769102B CN 202110903040 A CN202110903040 A CN 202110903040A CN 113769102 B CN113769102 B CN 113769102B
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cellulose
layer
polytetrafluoroethylene
functional carrier
solution
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CN113769102A (en
Inventor
吴水平
张磊
郑立新
周金生
李珺
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Shenzhen Huayuan Regeneration Medical Science Co ltd
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Shenzhen Huayuan Regeneration Medical Science Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38Cellulose; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/02Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/04Enzymes or microbial cells immobilised on or in an organic carrier entrapped within the carrier, e.g. gel or hollow fibres
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/02Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/08Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer
    • C12N11/082Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/02Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/10Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a carbohydrate
    • C12N11/12Cellulose or derivatives thereof

Abstract

The invention discloses a preparation method and application of a functional carrier bracket, wherein the functional carrier bracket comprises a substrate layer, a first cellulose layer and a first polytetrafluoroethylene layer which are sequentially laminated; the edge of the substrate layer and the edge of the first cellulose layer are bonded by a cellulose solution, and an opening is reserved; at least one cavity is formed between the substrate layer and the first cellulose layer. The functional carrier bracket with single or multiple cavities avoids the use of complex dies in the preparation method, and the preparation method is simple and efficient and expands the application field of the hydrogel.

Description

Preparation method and application of functional carrier bracket
Technical Field
The invention belongs to the technical field of medical appliances, and particularly relates to a preparation method and application of a functional carrier bracket.
Background
In the field of semipermeable membranes with a plurality of 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, and are widely applied to the fields of medicine extraction, protein separation, air filtration and the like. In addition, polytetrafluoroethylene (PTFE) semipermeable membranes have been used as vascular prostheses in the field of implantable biomedical materials.
The semipermeable membrane is packaged into a specific instrument structure so as to meet specific practical application requirements, which is a necessary link for the practical application of the semipermeable membrane. Such as the fixation of a filter cartridge in a water purifier and the encapsulation of a semipermeable membrane in a filter head. Besides being used for filtering consumable materials, the hydrogel film packaged into a specific capsule structure can also be used as a carrier for drug slow release and functional cell encapsulation. Thermal welding, ultrasonic welding, and glue bonding are currently the mainstream three film packaging processes, but the above methods are not applicable to the packaging of hydrogel films.
In addition, a complex mold is usually needed for preparing the hydrogel capsule with the cavity structure, and the process is complex. In particular to the preparation of ultra-thin hydrogel large capsules, and the requirement on the die precision 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 as follows:
A preparation method of the functional carrier bracket is provided.
The third technical problem to be solved by the invention is:
The application of the functional carrier bracket.
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 comprising a cellulose layer and a polytetrafluoroethylene layer.
In order to solve the first technical problem, the invention adopts the following technical scheme:
a functional carrier scaffold prepared from the cellulose/polytetrafluoroethylene composite hydrogel film described above, comprising:
The substrate layer, the first cellulose layer and the first polytetrafluoroethylene layer are sequentially laminated;
the edges of the substrate layer and the first cellulose layer are adhered by cellulose solution, and openings are reserved;
At least one cavity is formed between the substrate layer and the first cellulose layer.
According to one embodiment of the present invention, the method for preparing a cellulose solution includes: adding cotton linter into 7wt% NaOH and 12wt% urea aqueous solution, vibrating and dispersing, pre-cooling the system to below-12 ℃, rapidly stirring and dissolving at room temperature, centrifuging and removing bubbles to obtain cellulose solution.
According to one embodiment of the present invention, before the first cellulose layer and the first polytetrafluoroethylene layer are in contact with each other, a polytetrafluoroethylene porous film is laid on the surface of a glass sheet, the cellulose solution is poured into the surface layer of the polytetrafluoroethylene film by a tape casting method, and after further film scraping and standing treatment, the system is added into a coagulation bath to be gelled out, and finally the cellulose/polytetrafluoroethylene composite hydrogel film is obtained.
According to an embodiment of the present invention, the polytetrafluoroethylene is hydrophilic polytetrafluoroethylene to promote adhesion with the cellulose solution.
According to one embodiment of the present invention, the Polytetrafluoroethylene (PTFE) porous membrane has a pore size of 80nm to 8. Mu.m.
According to one embodiment of the present invention, the Polytetrafluoroethylene (PTFE) porous membrane has a thickness of 10 μm to 100. Mu.m.
According to one embodiment of the present invention, the Polytetrafluoroethylene (PTFE) porous membrane is a composite membrane with a support layer, and the support layer is PE, PP, PET.
According to an embodiment of the present invention, the thickness of the doctor blade is 20 μm to 200. Mu.m.
According to one embodiment of the present invention, the standing time is 1min to 1000min.
According to one embodiment of the invention, the coagulation bath is used in a solution of 10wt% to 100wt% aqueous ethanol.
According to one embodiment of the present invention, the gelation time is 0.01h to 10h.
According to one embodiment of the present invention, the base layer includes a second cellulose layer and a second polytetrafluoroethylene layer stacked and provided so as to be in contact with the first cellulose layer.
According to one embodiment of the present invention, at least one point of the second cellulose layer and the first cellulose layer at a non-edge is coated with a cellulose solution to form a plurality of communicating cavities between the second cellulose layer and the first cellulose layer.
Because the composite membrane has elasticity, when the solution is filled in the middle of the second cellulose layer and the first cellulose layer, the composite membrane can expand, so that the composite membrane becomes fragile, and when the cellulose solution is coated on at least one position of the non-edges of the second cellulose layer and the first cellulose layer, the cellulose solution can be adhered to the cellulose layer, so that a plurality of communicated cavities are formed in the middle of the second cellulose layer and the first cellulose layer, and the plurality of communicated cavities have structures, so that the expanded composite membrane cannot be expanded and split.
According to one embodiment of the invention, the matrix layer comprises a cellulose solution.
According to one embodiment of the present invention, the pores of the polytetrafluoroethylene film contain cellulose.
According to one embodiment of the present invention, the cellulose has a molecular weight of 10 to 1000 tens of thousands
According to one embodiment of the invention, the pore size of the polytetrafluoroethylene/cellulose composite membrane is in the range of 10-100nm.
In order to solve the second technical problem, the invention adopts the following technical scheme:
A method for preparing the functional carrier bracket, comprising the following steps:
And the first polytetrafluoroethylene layer, the first cellulose layer and the porous material are sequentially laminated, the cellulose solution is dripped into pores of the porous material, gelation is carried out after standing, 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, at least two cavities are formed on the peeled composite film, and the cavities are not contacted.
The multiple cavities which are not contacted and communicated can store different medicines or cell solutions, and when any cavity is broken carelessly, medicines or cells in other cavities are not affected.
According to one embodiment of the invention, the concentration of the above cellulose solution is between 0.5% and 60% by weight.
According to one embodiment of the present invention, the standing treatment time is 0.01h to 20h.
According to one embodiment of the present invention, the solution used for gelation is ethanol.
According to one embodiment of the present invention, the concentration of the aqueous ethanol solution is 1 wt% to 100wt%.
According to one embodiment of the present invention, the gelation time is 0.01h to 20h.
Hydrogels are aqueous materials whose pore structure can be controlled by cross-linking structure and density, and which function as semi-permeable membranes, and therefore hydrogels are widely used as carriers for cells or drugs. However, conventional hydrogel ultra-thin films (e.g., having a thickness of 50 μm or less) have poor strength and are easily curled, and are difficult to effectively apply in practice. The invention takes PTFE semipermeable membrane as a base material, and the pores of PTFE original membrane are regulated and controlled by compounding hydrogel on the surface layer. The thickness of the PTFE film can be regulated and controlled at will between 10 mu m and 100 mu m, and the thickness of the composite film of the invention can be 15 mu m or 100 mu m.
The surface layer of the PTFE film has only inert groups and no grafting sites. After the cellulose is introduced into the surface layer, the hydroxyl group of the surface layer is a reactive functional group and can be used as a grafting modification site. The hydroxyl can react with active components such as chlorinated hydrocarbon, epoxy and the like, for example, 2-bromoisobutyryl bromide is grafted on the hydroxyl by ATRP technology, and components such as zwitterions, amino acid and the like can be further grafted.
In a further aspect of the invention, there is also provided a carrier for sustained release of a drug, comprising a functional carrier scaffold as described above.
In a further aspect of the 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 easy to obtain. Cellulose is introduced into the pores of the polytetrafluoroethylene membrane, and active grafting sites can be introduced 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 the functional carrier support is filled with a drug solution or a cell solution, the middle part of the expanded functional carrier support cannot be expanded and cracked.
(3) When a plurality of cavities which are not communicated and are not contacted are formed in the functional carrier support, different medicines or cell solutions can be stored in each cavity, and medicines or cells in other cavities can not be influenced after any cavity is broken carelessly.
(4) The functional carrier bracket with single or multiple cavities avoids the use of complex dies in the preparation method, and the preparation method is simple and efficient and expands the application field of the hydrogel.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 is a functional carrier support object diagram.
FIG. 2 is a graph showing the mechanical properties of a cellulose/polytetrafluoroethylene hydrogel composite membrane.
Fig. 3 is a graph of permeability test of a cellulose/Polytetrafluoroethylene (PTFE) hydrogel composite membrane.
Detailed Description
Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout.
The embodiments described below by referring to the drawings are illustrative only and are not to be construed as limiting the invention.
In the description of the present invention, the description of the first, second, third, etc. is only for the purpose of distinguishing technical features, and should not be construed as indicating or implying a 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 references to orientation descriptions, such as directions of up, down, left, right, etc., are based on the orientation or positional relationship shown in the drawings, are merely for convenience of description and simplification of the description, and do not indicate or imply that the apparatus or element in question must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as limiting the invention.
In the description of the present invention, unless explicitly defined otherwise, terms such as arrangement, installation, connection, etc. should be construed broadly and the specific meaning of the terms in the present invention can be determined reasonably by a person skilled in the art in combination with the specific content of the technical solution.
In order to describe the technical contents, the achieved objects and effects of the present invention in detail, the following description will be made with reference to the embodiments.
Example 1
1) 40G of a mixed solution of 7wt% NaOH and 12wt% urea is prepared, 10g of cotton linter cellulose with a molecular weight of 100 ten thousand Da is added into the mixed solution, and vibration dispersion is carried out. Then the system is frozen and preserved for 10 hours at the temperature of minus 20 ℃, and is rapidly stirred and dissolved to a transparent and clear state at room temperature, and air bubbles are removed by centrifugation, thus obtaining 20wt% cellulose solution;
2) A hydrophilic Polytetrafluoroethylene (PTFE) porous film with a thickness of 40 μm and a pore diameter of 220nm is laid on the surface of a glass sheet, the cellulose solution is poured into the surface layer of the Polytetrafluoroethylene (PTFE) film, and a bar coater with a thickness of 54.9 μm is used for scraping the film. Then standing for 5 hours, adding the system into a coagulating bath of 50wt% ethanol water solution for gelatinizing for 3 hours, and finally obtaining the cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel film.
Example 2
1) 30G of a mixed solution of 7wt% NaOH/12wt% urea is prepared, 10g of cotton linter cellulose with a molecular weight of 200 ten thousand Da is added into the mixed solution, and the mixed solution is fully vibrated and dispersed. Then the system is frozen and preserved for 10 hours at the temperature of minus 20 ℃, and is rapidly stirred and dissolved to a transparent and clear state at room temperature, and air bubbles are removed by centrifugation, so as to obtain a 15wt% cellulose solution;
2) The cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel film (with one side of the cellulose film facing upwards) prepared according to the method is laid on a glass plate, and 10wt% cellulose solution is slowly extruded on specific sites on the surface of the cellulose film at a speed of 1ml/min by adopting a micro peristaltic pump. Then another piece of cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel film (with the cellulose side facing downwards) was laid on the surface of the composite film, and left standing for 1h. And finally, placing the composite membrane in a 20wt% ethanol water solution for gelation for 2 hours, and washing the composite membrane with a large amount of deionized water for multiple times to obtain the cellulose/Polytetrafluoroethylene (PTFE) composite hydrogel large bracket with a cavity structure. The central hydrogel cavity may be used for drug or cell encapsulation.
Example 3
1) Preparing 45g of 7wt% NaOH/12wt% urea mixed solution, adding 5g of cotton linter cellulose with a molecular weight of 50 ten thousand Da into the mixed solution, fully vibrating and dispersing, then freezing and preserving the system at-20 ℃ for 10 hours, rapidly stirring and dissolving the system at room temperature to a transparent and clear state, centrifuging to remove bubbles, and obtaining 10wt% cellulose solution;
2) Pouring the cellulose solution into a mold, spreading the 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, smoothing with a glass rod, standing for 2h, performing gelation treatment in a 30wt% ethanol coagulation bath for 2h, washing with a large amount of deionized water for multiple times, and finally obtaining the multi-cavity structure cellulose composite bracket, wherein the surface layer of the multi-cavity structure cellulose composite bracket is covered with a layer of the Polytetrafluoroethylene (PTFE)/cellulose composite film, so that the closed multi-cavity structure cellulose composite bracket is formed.
FIG. 2 is a graph showing the mechanical properties of a cellulose/polytetrafluoroethylene hydrogel composite membrane.
As can be seen from fig. 2, the strength and flexibility (elongation) of the composite film are improved as compared to the PTFE film and the cellulose film of a single component.
Fig. 3 is a graph of permeability test of a cellulose/Polytetrafluoroethylene (PTFE) hydrogel composite membrane.
As can be seen from the permeation efficiency graph of the composite membrane, the composite membrane can efficiently intercept macromolecules such as IgG of 150kDa and the like, and the permeation rate can be controlled within 5%; at the same time, the osmotic filtration of the 10kDa FITC-dextran small molecule is not affected, which shows that the composite membrane is a semipermeable membrane which can aim at a specific molecular weight substance.
The foregoing is merely exemplary embodiments of the present invention and are not intended to limit the scope of the present invention, and all equivalent modifications made by the present invention or direct or indirect application in the relevant art are intended to be included in the scope of the present invention.

Claims (3)

1. A functional carrier bracket for preparing a cellulose/polytetrafluoroethylene composite hydrogel film is characterized in that:
Comprises a basal body layer, a first cellulose layer and a first polytetrafluoroethylene layer which are sequentially laminated;
the substrate layer comprises a second cellulose layer and a second polytetrafluoroethylene layer which are stacked, the edges of the second cellulose layer and the first cellulose layer are adhered by cellulose solution, and openings are reserved;
At least one point of the non-edges of the second cellulose layer and the first cellulose layer is coated with a cellulose solution so as to form a plurality of communicated cavities between the second cellulose layer and the first cellulose layer;
A method of preparing a functional carrier scaffold comprising the steps of:
Spreading a matrix layer on a glass plate, slowly extruding 10wt% cellulose solution on at least one part of the surface of a second cellulose layer, which is not at the edge, by adopting a micro peristaltic pump at a speed of 1ml/min, spreading a first cellulose layer and a first polytetrafluoroethylene layer on the surface of the matrix layer, standing for 1h to obtain a composite membrane, and finally placing the composite membrane in 20wt% ethanol water solution for gelatinization for 2h, and washing for multiple times by using deionized water to obtain the functional carrier bracket.
2. A carrier for sustained release of a drug, characterized in that: comprising a functional carrier support according to claim 1.
3. A cell carrier, characterized in that: comprising a functional carrier support according to claim 1.
CN202110903040.7A 2021-08-06 2021-08-06 Preparation method and application of functional carrier bracket Active CN113769102B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0747046A2 (en) * 1995-05-19 1996-12-11 Baxter International Inc. Permeable immunoisolation membrane structures for implantation of cells in host tissue
CN107417979A (en) * 2017-09-02 2017-12-01 天津科技大学 A kind of gelatinous fibre element composite membrane and preparation method thereof
KR20210056472A (en) * 2019-11-08 2021-05-20 한양대학교 에리카산학협력단 Oxidized cellulose based-multilayered nanoemulsion film and use thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040105880A1 (en) * 2002-11-21 2004-06-03 Turner Josephine Sara Interpenetrating polymer network

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0747046A2 (en) * 1995-05-19 1996-12-11 Baxter International Inc. Permeable immunoisolation membrane structures for implantation of cells in host tissue
CN107417979A (en) * 2017-09-02 2017-12-01 天津科技大学 A kind of gelatinous fibre element composite membrane and preparation method thereof
KR20210056472A (en) * 2019-11-08 2021-05-20 한양대학교 에리카산학협력단 Oxidized cellulose based-multilayered nanoemulsion film and use thereof

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