CN107854723A - A kind of hydrogel of preventing tissue adhesion and preparation method thereof - Google Patents

A kind of hydrogel of preventing tissue adhesion and preparation method thereof Download PDF

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Publication number
CN107854723A
CN107854723A CN201711113486.XA CN201711113486A CN107854723A CN 107854723 A CN107854723 A CN 107854723A CN 201711113486 A CN201711113486 A CN 201711113486A CN 107854723 A CN107854723 A CN 107854723A
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hydrogel
tissue adhesion
preventing tissue
preparation
parts
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全大萍
冯文娟
孟月
杜钊夷
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Sun Yat Sen University
National Sun Yat Sen University
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National Sun Yat Sen University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/008Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0014Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/0066Medicaments; Biocides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a kind of hydrogel of preventing tissue adhesion and preparation method thereof, the hydrogel is um porous structure;0.1~100 part of 0.1~100 part of hydroxyethyl methacrylate, 0.1~27 part of crosslinking agent, 0.1~1.5 part of tetramethylethylenediamine, 0.1~2 part of initiator and water.The hydrogel of the preventing tissue adhesion of the present invention has um porous structure, can be used for loading the composition that trophic factors, medicine etc. promote surface of a wound regeneration and reparation, accelerating wound healing, adhesion wound, to cell without adhesiveness, have good preventing tissue adhesion performance.

Description

A kind of hydrogel of preventing tissue adhesion and preparation method thereof
Technical field
The present invention relates to medical material technical field, in particular to a kind of hydrogel and its system of preventing tissue adhesion Preparation Method.
Background technology
Wound is the defect or broken of human body skin, mucous membrane, tissue because of physics, mechanically or thermally caused by the extraneous factor such as power Ring, the healing of general wound are divided into inflammation, granulation tissue formation, matrix rebuilding phase, cicatrization four periods of healing, each period Healing state and last length except having outside the Pass with patient itself age, neuroendocrine and Immunity, also with surface of a wound office Relevant such as hemotoncus, the slough presence of portion's factor, local application, local external environment (mainly moistening degree, gradient of infection) Relevant, the often treatment for the surface of a wound is to help the surface of a wound to be cured from its Local physical or chemical environment is improved using appropriate dressing Close.
From wound healing mechanism and require, the dressing in ideal is except the work with the protection anti-secondary insult of the surface of a wound With outer, it is also necessary to have water holding moisturizing even debridement, promote the Biofunctionals such as granulation tissue regeneration, antibacterial and act on, and current city Traditional dressing such as gauze on face is not only opaque and stops the less effective of foreign pathogen, and retentiveness difference can not be built Moist environment, fiber are easy to fall off, dressing in itself easily and tissue adhesion, this just easily brings pain even to patient in more change dressings Secondary damage.
At present, with the development that materialogy and industry are learned, synthetic dressing is widely used in the treatment reparation of the surface of a wound.Its In, film-type dressing is transparent to be beneficial to observation, and good permeability is close with tissue surface bonding, but can not absorb diffusate and then product Trigger infection under film;Foam type dressing has loose structure, and absorbability is strong, and moisture permeability is high, but because hole is larger, is easy to Adherent cell, new granulation tissue, which easily grows into, causes secondary damage, and increases surface of a wound scar with foam scrap is left;Hydrocolloid The absorbable few sepage to middle amount of class dressing, has part debridement effect, but it is opaque, belongs to complete seal;Hydrogel applies Material is a kind of new pattern compress to grow up in recent years, hydrogel be it is a kind of formed by various crosslinking methods it is water-soluble or close Waterborne polymeric, water absorbing capacity is strong, can continuous absorption wound exudate, accelerate epithelial cell growth, accelerate new capilary to regenerate, support Antibacterium is invaded, and prevents wound infection.Tissue adhesion's property of existing aerogel dressing is still higher, generally requires to coat on its surface Layer of material could realize preferable tissue sticking resistant performance.
The content of the invention
In view of this, hydrogel of a kind of preventing tissue adhesion provided by the invention and preparation method thereof, preferably overcomes The above-mentioned problems of the prior art and defect, the hydrogel of the preventing tissue adhesion have um porous structure, can be used for bearing Carry trophic factors, medicine etc. and promote surface of a wound regeneration and the composition repaired, accelerating wound healing, adhesion wound, to cell without viscous Attached property, there is good preventing tissue adhesion performance;In addition, the hydrogel has good biocompatibility, without obvious cell toxicant Property;The material softness, all wounds can be closely covered, resist bacterial invasion, avoid trauma surface infestation.
A kind of hydrogel of preventing tissue adhesion, the hydrogel are um porous structure;For forming the hydrogel Raw materials by weight portion meter includes:0.1~100 part of hydroxyethyl methacrylate, 0.1~27 part of crosslinking agent, tetramethylethylenediamine 0.1~100 part of 0.1~1.5 part, 0.1~2 part of initiator and water.
Further, the raw material is also included in terms of parts by weight:0.05~3 part of carboxymethyl cellulose.
Further, the crosslinking agent is polyethyleneglycol diacrylate, ethylene glycol dimethacrylate and three second two One kind in alcohol dimethylacrylate.
Further, the crosslinking agent is polyethyleneglycol diacrylate, the molecule of the polyethyleneglycol diacrylate Measure as 600~10000.
Further, the initiator is ammonium persulfate.
Present invention also offers a kind of preparation method of the hydrogel of preventing tissue adhesion, the hydrogel of the preventing tissue adhesion For the hydrogel of above-mentioned preventing tissue adhesion, the preparation method includes:
Hydroxyethyl methacrylate, crosslinking agent, tetramethylethylenediamine and water are first well mixed, initiator is then added and mixes Close uniformly, obtain mixed liquor;
The mixed liquor is subjected to confined reaction, after reaction terminates, obtained hydrogel washed.
Further, before the mixed liquor is carried out into confined reaction, first the mixed liquor is carried out ultrasonic 10s~ 180s。
Further, the time of the confined reaction is 0.5~48h;The temperature of the confined reaction is 20~80 DEG C.
Further, the confined reaction includes:3h is first reacted at 23~27 DEG C, then 24h is reacted at 60 DEG C.
Further, the washing includes:By hydrogel immersion 6~15 days in deionized water, water two was changed daily It is secondary.
Compared with prior art, the beneficial effect of hydrogel of a kind of preventing tissue adhesion of the invention and preparation method thereof It is:
1st, the hydrogel of preventing tissue adhesion of the invention, has um porous structure, can be used for loading trophic factors, medicine Thing etc. promotes surface of a wound regeneration and the composition repaired, accelerating wound healing, adhesion wound, to cell without adhesiveness;Meanwhile its group It is controllable to knit adhesiveness, its mechanical strength is controllable in 20000~80000Pa.
2nd, the hydrogel water absorbing properties of preventing tissue adhesion of the invention can adjust, and can be selected according to the requirement of the different surface of a wound The absorbed wound exudate of different water absorbing properties, avoid sepage gather and caused by wound infection.
3rd, the transparency of the hydrogel of preventing tissue adhesion of the invention can be by adjusting hydroxyethyl methacrylate and water Ratio regulate and control, required according to the observation of wound healing, select the aerogel dressing of different material ratio, transparent hydrogel Dressing is beneficial to the situation for observing surface of a wound vascularization and granulation regeneration in use.
4th, the hydrogel of preventing tissue adhesion of the invention has good biocompatibility, without obvious cytotoxicity;The material Material is soft, can closely cover all wounds, resists bacterial invasion, avoids trauma surface infestation.
5th, further, the hydrogel of preventing tissue adhesion of the invention can be according to the different demands of clinic, by adding not With molecular weight linkers and carboxymethyl cellulose is added, prepares the hydrogel of the preventing tissue adhesion of different performance.
To enable the above objects, features and advantages of the present invention to become apparent, preferred embodiment cited below particularly, and coordinate Appended accompanying drawing, is described in detail below.
Brief description of the drawings
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below by embodiment it is required use it is attached Figure is briefly described, it will be appreciated that the following drawings illustrate only certain embodiments of the present invention, therefore be not construed as pair The restriction of scope, for those of ordinary skill in the art, on the premise of not paying creative work, can also be according to this A little accompanying drawings obtain other related accompanying drawings.
SEM figure (the amplifications 200 that Fig. 1 is the hydrogel p (HEMA-co-PEG10k) that the embodiment of the present invention 1 is prepared Times);
SEM figure (the amplifications 1500 that Fig. 2 is the hydrogel p (HEMA-co-PEG10k) that the embodiment of the present invention 1 is prepared Times);
The SEM figures that Fig. 3 is the hydrogel p (HEMA-co-PEG0.6k-PEG10k) that the embodiment of the present invention 3 is prepared (are put It is big 200 times);
The SEM figures that Fig. 4 is the hydrogel p (HEMA-co-PEG0.6k-PEG10k) that the embodiment of the present invention 3 is prepared (are put It is big 1500 times);
Fig. 5 is the hydrogel p (HEMA-co-PEG10k) that is prepared of the embodiment of the present invention 1, embodiment 2 is prepared The hydrogel p's (HEMA-co-PEG0.6k-PEG10k) that hydrogel p (HEMA-co-PEG0.6k) and embodiment 3 are prepared Mechanical strength test chart;
Fig. 6 is the hydrogel p (HEMA-co-PEG10k) that is prepared of the embodiment of the present invention 1, prepared by the embodiment of the present invention 3 Obtained hydrogel p (HEMA-co-PEG0.6k-PEG10k) and the cell of bacteria cellulose (BC) hydrogel co-cultures activity and surveyed Attempt;
Fig. 7 is the cell adherence for the hydrogel p (HEMA-co-PEG0.6k-PEG10k) that the embodiment of the present invention 3 is prepared Property experiment DAPI coloration result figures;
The cell adhesion experiment that Fig. 8 is the hydrogel p (HEMA-co-PEG10k) that the embodiment of the present invention 1 is prepared DAPI coloration result figures;
Fig. 9 is the DAPI coloration result figures that the cell adhesion of bacteria cellulose (BC) hydrogel is tested;
Figure 10 is the DAPI coloration result figures that the cell adhesion of thick gauze is tested;
Figure 11 is the transparency observation figure for the hydrogel that embodiment 2 and embodiment 4~8 are prepared.
Embodiment
For the ease of understanding the present invention, technical scheme is elaborated with reference to the mode of embodiment, Many details are elaborated in the following description in order to fully understand the present invention.
But the invention can be embodied in many other ways as described herein, those skilled in the art can be with Similar improvement is done in the case of without prejudice to intension of the present invention, therefore the present invention is not limited to the specific embodiments disclosed below.
Unless otherwise defined, all technologies used herein and scientific terminology have and the common skill of art of the present invention The identical implication that art personnel are generally understood that.When contradiction be present, the definition in this specification is defined.
Term as used herein:
" by ... prepare " it is synonymous with "comprising".Term "comprising" used herein, " comprising ", " having ", " containing " Or its any other deformation, it is intended that cover including for non-exclusionism.For example, composition, step, method comprising listed elements, Product or device are not necessarily limited to those key elements, but can include not expressly listed other key elements or such a composition, step Suddenly, method, product or the intrinsic key element of device.
Conjunction " by ... form " exclude any key element do not pointed out, step or component.If be used in claim, This phrase will make claim be closed, it is not included the material in addition to the material of those descriptions, but relative Except customary impurities.When phrase " by ... form " be rather than immediately following theme in the clause that appears in claim main body after When, it is only limited to the key element described in the clause;Other key elements be not excluded as entirety the claim it Outside.
Equivalent, concentration or other values or parameter are excellent with scope, preferred scope or a series of upper limit preferred values and lower limit During the Range Representation that choosing value limits, this, which is appreciated that, specifically discloses by any range limit or preferred value and any scope All scopes that any pairing of lower limit or preferred value is formed, regardless of whether the scope separately discloses.For example, when open Scope " when 1~5 ", described scope should be interpreted as including scope " 1~4 ", " 1~3 ", " 1~2 ", " 1~2 and 4~ 5 ", " 1~3 and 5 " etc..When number range is described herein, unless otherwise indicated, otherwise the scope is intended to include its end Value and all integers and fraction within the range.
"and/or" is used to represent that one of illustrated situation or both may to occur, for example, A and/or B includes (A And B) and (A or B);
The invention provides a kind of hydrogel of preventing tissue adhesion, the gel is um porous structure;For being formed Stating the raw materials by weight portion meter of gel includes:
0.1~100 part of hydroxyethyl methacrylate (HEMA) as 0.1 part, 0.5 part, 1 part, 5 parts, 10 parts, 20 parts, 30 parts, 50 parts, 80 parts or 100 parts etc.;
0.1~27 part of crosslinking agent is such as 0.1 part, 0.5 part, 1 part, 5 parts, 10 parts, 15 parts, 20 parts, 23 parts, 25 parts or 27 parts Deng;
0.1~1.5 part of tetramethylethylenediamine (TEMED) is such as 0.1 part, 0.2 part, 0.5 part, 0.8 part, 1 part, 1.2 parts or 1.5 Part etc.;
Such as 0.1 part, 0.2 part, 0.5 part, 0.8 part, 1 part, 1.2 parts, 1.5 parts, 1.8 parts or 2 parts of 0.1~2 part of initiator;
With such as 0.1 part, 0.5 part, 1 part, 5 parts, 10 parts, 20 parts, 30 parts, 50 parts, 80 parts or 100 parts of 0.1~100 part of water Deng.
Further, the raw material is also included in terms of parts by weight:Such as 0.05 part of 0.05~3 part of carboxymethyl cellulose, 0.5 Part, 1 part, 1.5 parts, 2 parts, 2.5 parts or 3 parts etc..
Further, the crosslinking agent is polyethyleneglycol diacrylate (PEGDA), ethylene glycol dimethacrylate (EDMA), one kind in TEGDMA (TEGDA).
Further, the crosslinking agent is polyethyleneglycol diacrylate (PEGDA), the polyethyleneglycol diacrylate Molecular weight for 600~10000 such as 600,800,1000,2000,3000,4000,5000,6000,7000,8000,9000 or 10000 etc..Following PEGDA-10k are the polyethyleneglycol diacrylate that molecular weight is 10000, and PEGDA-0.6k is molecule Measure the polyethyleneglycol diacrylate for 600.
Further, the initiator is ammonium persulfate (APS) solution.
Present invention also offers a kind of preparation method of the hydrogel of preventing tissue adhesion, the hydrogel of the preventing tissue adhesion For the hydrogel of above-mentioned preventing tissue adhesion, the preparation method includes:
Hydroxyethyl methacrylate, crosslinking agent, tetramethylethylenediamine and water are first well mixed, initiator is then added and mixes Close uniformly, obtain mixed liquor;
The mixed liquor is subjected to confined reaction, after reaction terminates, obtained hydrogel washed.
Further, before the mixed liquor is carried out into confined reaction, first the mixed liquor is carried out ultrasonic 10s~ 180s。
Further, the time of the confined reaction be 0.5~48h such as 0.5h, 1h, 3h, 5h, 10h, 15h, 20h, 25h, 30h, 35h, 40h, 45h or 48h etc.;The temperature of the confined reaction be 20~80 DEG C as 20 DEG C, 25 DEG C, 30 DEG C, 40 DEG C, 50 DEG C, 60 DEG C, 70 DEG C or 80 DEG C etc..
Further, the confined reaction includes:First at 23~27 DEG C such as 23 DEG C, 24 DEG C, 25 DEG C, 26 DEG C or 27 DEG C 3h is reacted, then 24h is reacted at 60 DEG C.
Further, the washing includes:By the hydrogel immersion in deionized water 6~15 days as 6 days, 8 days, 10 My god, 12 days or 15 days etc., change water daily twice.
For the ease of understanding the present invention, technical scheme is further illustrated with reference to embodiment.Applicant Statement, the present invention are illustrated by the following examples detailed process equipment and the technological process of the present invention, but not office of the invention It is limited to these specific process equipments and technological process, that is, does not mean that the present invention should rely on following detailed process equipments and technique Flow could be implemented.Person of ordinary skill in the field is each to product of the present invention it will be clearly understood that any improvement in the present invention The equivalence replacement of raw material and the addition of auxiliary element, the selection of concrete mode etc., all fall within protection scope of the present invention and openly Within the scope of.
Embodiment 1
A kind of preparation method of the hydrogel of preventing tissue adhesion is as follows:
(1) 25 parts of hydroxyethyl methacrylates are dissolved in 75 parts of water, then sequentially add 25 parts of molecular weight as 10000 Polyethyleneglycol diacrylate (PEGDA-10k), 0.375 part of tetramethylethylenediamine and 0.5 part of ammonium persulfate solution, acutely shake Swing well mixed, obtain mixed liquor.
(2) after above-mentioned mixed liquor ultrasound is removed bubble in 1 minute, it is injected into the glass mold that interior thickness is 0.5mm In;Then first react at room temperature 3 hours, then reacted 24 hours at a temperature of 60 DEG C in confined conditions.
(3) after above-mentioned reaction terminates, obtained hydrogel is soaked into fortnight in deionized water, changes water daily twice, Obtain hydrogel p (HEMA-co-PEG10k).
Embodiment 2
(1) 55 parts of hydroxyethyl methacrylates are dissolved in 45 parts of water, then sequentially add 1.76 parts of molecular weight as 600 Polyethyleneglycol diacrylate (PEGDA-0.6k), 0.825 part of tetramethylethylenediamine and 1.1 parts of ammonium persulfate solutions, acutely Concussion is well mixed, obtains mixed liquor.
(2) after above-mentioned mixed liquor ultrasound is removed bubble in 1 minute, it is injected into the glass mold that interior thickness is 0.5mm In;Then first react at room temperature 3 hours, then reacted 24 hours at a temperature of 60 DEG C in confined conditions.
(3) after above-mentioned reaction terminates, obtained hydrogel is soaked into fortnight in deionized water, changes water daily twice, Obtain hydrogel p (HEMA-co-PEG0.6k).
Embodiment 3
(1) 42 parts of hydroxyethyl methacrylates are dissolved in 58 parts of water, then sequentially add 1.4 parts of molecular weight as 600 Polyethyleneglycol diacrylate (PEGDA-0.6k), the polyethyleneglycol diacrylate (PEGDA- that 11 parts of molecular weight are 10000 10k), 0.63 part of tetramethylethylenediamine and 0.84 part of ammonium persulfate solution, acutely concussion is well mixed, obtains mixed liquor.
(2) after above-mentioned mixed liquor ultrasound is removed bubble in 1 minute, it is injected into the glass mold that interior thickness is 0.5mm In;Then first react at room temperature 3 hours, then reacted 24 hours at a temperature of 60 DEG C in confined conditions.
(3) after above-mentioned reaction terminates, obtained hydrogel is soaked into fortnight in deionized water, changes water daily twice, Obtain hydrogel p (HEMA-co-PEG0.6k-PEG10k).
Embodiment 4
Difference with embodiment 2 is:35 parts of hydroxyethyl methacrylates are dissolved in 65 parts of water.
Embodiment 5
Difference with embodiment 2 is:40 parts of hydroxyethyl methacrylates are dissolved in 60 parts of water.
Embodiment 6
Difference with embodiment 2 is:45 parts of hydroxyethyl methacrylates are dissolved in 55 parts of water.
Embodiment 7
Difference with embodiment 2 is:50 parts of hydroxyethyl methacrylates are dissolved in 50 parts of water.
Embodiment 8
Difference with embodiment 2 is:60 parts of hydroxyethyl methacrylates are dissolved in 40 parts of water.
Embodiment 9
Difference with embodiment 1 is:In step (1), first 25 parts of hydroxyethyl methacrylates are dissolved in 75 parts of water, Then 0.05 part of carboxymethyl cellulose is sequentially added, the polyethyleneglycol diacrylate (PEGDA- that 25 parts of molecular weight are 10000 10k), 0.375 part of tetramethylethylenediamine and 0.5 part of ammonium persulfate solution, acutely concussion is well mixed, obtains mixed liquor.
Embodiment 10
Difference with embodiment 2 is:In step (1), first 55 parts of hydroxyethyl methacrylates are dissolved in 45 parts of water, Then 0.5 part of carboxymethyl cellulose is sequentially added, the polyethyleneglycol diacrylate (PEGDA- that 1.76 parts of molecular weight are 600 0.6k), 0.825 part of tetramethylethylenediamine and 1.1 parts of ammonium persulfate solutions, acutely concussion is well mixed, obtains mixed liquor.
Embodiment 11
Difference with embodiment 3 is:In step (1), 42 parts of hydroxyethyl methacrylates are dissolved in 58 parts of water, so 1 part of carboxymethyl cellulose, the polyethyleneglycol diacrylate (PEGDA-0.6k) that 1.4 parts of molecular weight are 600,11 are sequentially added afterwards Polyethyleneglycol diacrylate (PEGDA-10k), 0.63 part of tetramethylethylenediamine and the 0.84 part of over cure that part molecular weight is 10000 Acid ammonium solution, acutely concussion is well mixed, obtains mixed liquor.
The hydrogel that Example 1 and embodiment 3 are prepared carries out following scanning electron microscopy as test sample Mirror, cell co-culture activity and organizational coherence test;And the hydrogel that Example 1~3 is prepared enters as test sample The following rheologic behavio(u)r of row and equilibrium swelling ratio test.
1st, scanning electron microscope test:
The hydrogel p (HEMA-co-PEG10k) that embodiment 1 is prepared observes what is obtained under a scanning electron microscope As depicted in figs. 1 and 2, the hydrogel p (HEMA-co-PEG0.6k-PEG10k) that embodiment 3 is prepared is in scanning electron for structure The structure that micro- Microscopic observation obtains is as shown in Figure 3 and Figure 4.The water-setting that embodiment 1 is prepared it can be seen from Fig. 1 to Fig. 4 The hydrogel p (HEMA-co-PEG0.6k-PEG10k) that glue p (HEMA-co-PEG10k) and embodiment 3 are prepared is respectively provided with micro- Rice loose structure.Two kinds of hydrogels are contrasted, low power scanning issues the hydrogel p (HEMA-co- that current embodiment 3 is prepared PEG0.6k-PEG10k) microcellular structure for the hydrogel p (HEMA-co-PEG10k) being prepared compared to embodiment 1 is more loose, High power scanning issues the micropore size increase for the hydrogel p (HEMA-co-PEG0.6k-PEG10k) that current embodiment 3 is prepared, The micropore diameter of hydrogel can be increased by illustrating the addition of the small crosslinking agent of molecular weight.
2nd, rheology testing result is as shown in Figure 5:
The mechanical strength for the hydrogel p (HEMA-co-PEG10k) that embodiment 1 is prepared is 20000Pa, and embodiment 2 is made Standby obtained hydrogel p (HEMA-co-PEG0.6k) mechanical strength has reached 80000Pa, the water-setting that embodiment 3 is prepared Glue p (HEMA-co-PEG0.6k-PEG10k) mechanical strength is 46000Pa or so, illustrates to improve the small crosslinking agent of molecular weight PEGDA-0.6k content can strengthen the mechanical property of hydrogel.
3rd, equilibrium swelling ratio is tested:
Method of testing is:Weight, which is weighed, after the hydrogel prepared is freeze-dried is designated as W0, then it is immersed in deionized water In, different time points are taken out, and are weighed after wiping surface water drops with filter paper and are designated as W1, until hydrogel water suction reaches counterpoise not Change is designated as Wt.The calculating publicity of swelling ratio is:
Swelling ratio=(W1-W0)/W0
Equilibrium swelling ratio=(Wt-W0)/W0
It can be obtained by above-mentioned method of testing:Hydrogel p (the HEMA-co-PEG0.6k- that embodiment 3 is prepared PEG10k the hydrogel p that hydrogel p (HEMA-co-PEG10k) that), embodiment 1 is prepared, embodiment 2 are prepared (HEMA-co-PEG0.6k) equilibrium swelling ratio is respectively 286%, 610%, 85%, the water-setting that embodiment 9~11 is prepared The equilibrium swelling ratio of glue is respectively 769%, 332% and 487%, illustrates to improve containing for the big crosslinking agent PEGDA-10k of molecular weight Amount can increase the water absorbing properties of hydrogel, and addition carboxymethyl cellulose (CMC) can further improve hydrogel in preparation process Water absorbing properties.
4th, it is as shown in Figure 6 to co-culture active testing for cell:
Using bacteria cellulose (BC) hydrogel more commonly used on the market as control group, embodiment 1 is prepared respectively Hydrogel p (HEMA-co-PEG10k), the hydrogel p (HEMA-co-PEG0.6k-PEG10k) that is prepared of embodiment 3 and Bacteria cellulose (BC) hydrogel of control group carries out cell and co-cultures active testing, the results showed that the cell of three kinds of hydrogels is lived Property more than 85%, illustrate by the hydrogel that the embodiment of the present invention is prepared without obvious cell co-culture activity, biofacies Capacitive is preferable.
5th, organizational coherence test result is as shown in Figure 7 to 10:
Hydrogel p (HEMA-co-PEG0.6k-PEG10k) that embodiment 3 is prepared, embodiment 1 are prepared into respectively Four kinds of hydrogel p (HEMA-co-PEG10k), BC hydrogels and thick the gauze materials arrived carry out DAPI dyeing, as a result respectively as schemed 7th, shown in Fig. 8, Fig. 9 and Figure 10, hydrogel p (HEMA-co-PEG10k) and embodiment 3 that embodiment 1 is prepared are prepared Hydrogel p (HEMA-co-PEG0.6k-PEG10k) adherent cell it is less, but the hydrogel p that embodiment 3 is prepared (HEMA-co-PEG0.6k-PEG10k) adherent cell on is than hydrogel p (HEMA-co- that embodiment 1 is prepared PEG10k) to lack, BC hydrogels and thick gauze group adherent cell are then a lot, and thick gauze group cell is along the intensive life of string It is long.It can be said that the hydrogel that the bright embodiment of the present invention is prepared is unfavorable for sticking for cell, and the friendship that molecular weight is small The introducing of connection agent can further weaken tissue adhesion's property of hydrogel.
The hydrogel that embodiment 2 and embodiment 4~8 are prepared carries out transparency observation, H1, H2, H3, H4, H5 and H6 represents the hydrogel that embodiment 8, embodiment 2, embodiment 7, embodiment 6, embodiment 5 and embodiment 4 are prepared respectively, surveys Test result is as shown in figure 11:With HEMA content increase, the transparency increase of hydrogel, illustrate that the raising of HEMA contents can Increase the transparency of hydrogel.

Claims (10)

  1. A kind of 1. hydrogel of preventing tissue adhesion, it is characterised in that:The hydrogel is um porous structure;It is described for being formed The raw materials by weight portion meter of hydrogel includes:0.1~100 part of hydroxyethyl methacrylate, 0.1~27 part of crosslinking agent, tetramethyl 0.1~100 part of 0.1~1.5 part of base ethylenediamine, 0.1~2 part of initiator and water.
  2. 2. the hydrogel of preventing tissue adhesion according to claim 1, it is characterised in that:The raw material is gone back in terms of parts by weight Including:0.05~3 part of carboxymethyl cellulose.
  3. 3. the hydrogel of preventing tissue adhesion according to claim 1, it is characterised in that:The crosslinking agent is polyethylene glycol two One kind in acrylate, ethylene glycol dimethacrylate and TEGDMA;The polyethylene glycol two The molecular weight of acrylate is 600~10000.
  4. 4. the hydrogel of preventing tissue adhesion according to claim 3, it is characterised in that:The crosslinking agent is polyethylene glycol two Acrylate, the molecular weight of the polyethyleneglycol diacrylate is 600~10000.
  5. 5. the hydrogel of preventing tissue adhesion according to claim 1, it is characterised in that:The initiator is ammonium persulfate.
  6. A kind of 6. preparation method of the hydrogel of preventing tissue adhesion, it is characterised in that:The hydrogel of the preventing tissue adhesion is such as The hydrogel of preventing tissue adhesion described in any one of Claims 1 to 5, the preparation method include:
    Hydroxyethyl methacrylate, crosslinking agent, tetramethylethylenediamine and water are first well mixed, it is equal then to add initiator mixing It is even, obtain mixed liquor;
    The mixed liquor is subjected to confined reaction, after reaction terminates, obtained hydrogel washed.
  7. 7. the preparation method of the hydrogel of preventing tissue adhesion according to claim 6, it is characterised in that:By the mixing Before liquid carries out confined reaction, ultrasonic 10s~180s first is carried out to the mixed liquor.
  8. 8. the preparation method of the hydrogel of preventing tissue adhesion according to claim 6, it is characterised in that:The confined reaction Time be 0.5~48h;The temperature of the confined reaction is 20~80 DEG C.
  9. 9. the preparation method of the hydrogel of preventing tissue adhesion according to claim 8, it is characterised in that:The confined reaction Including:3h is first reacted at 23~27 DEG C, then 24h is reacted at 60 DEG C.
  10. 10. the preparation method of the hydrogel of preventing tissue adhesion according to claim 6, it is characterised in that:The washing bag Include:By hydrogel immersion in deionized water, 6~15 days, water is changed daily twice.
CN201711113486.XA 2017-11-13 2017-11-13 A kind of hydrogel of preventing tissue adhesion and preparation method thereof Pending CN107854723A (en)

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Application publication date: 20180330