CN106397674A - Temperature-sensitive postoperative adhesion cellulose modifying material and preparation method and application thereof - Google Patents

Temperature-sensitive postoperative adhesion cellulose modifying material and preparation method and application thereof Download PDF

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CN106397674A
CN106397674A CN201610846952.4A CN201610846952A CN106397674A CN 106397674 A CN106397674 A CN 106397674A CN 201610846952 A CN201610846952 A CN 201610846952A CN 106397674 A CN106397674 A CN 106397674A
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thermo
sensitive
preparation
adhesion
modified material
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CN106397674B (en
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张黎明
张俊钊
李海量
黄雅清
谢民强
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Southern Medical University Zhujiang Hospital
National Sun Yat Sen University
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Southern Medical University Zhujiang Hospital
National Sun Yat Sen University
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    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08FMACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F251/00Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
    • C08F251/02Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof on to cellulose or derivatives thereof
    • 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
    • A61L26/008Hydrogels 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
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/009Materials resorbable by the body
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04Macromolecular materials
    • A61L31/042Polysaccharides
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/145Hydrogels 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148Materials at least partially resorbable by the body

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Abstract

The invention discloses a temperature-sensitive postoperative adhesion cellulose modifying material and a preparation method and application thereof. Sulfobetaines type zwitterionic monomers with anti-cell-adhesion or protein non-specificity adsorption property are grafted and co-polymerized onto a temperature-sensitive methylcellulose main chain, and a grafted copolymer aqueous solution is prepared by a low-temperature dissolution method. At the room temperature, the grafted copolymer aqueous solution is viscous liquid which is easy to inject or coat, can become hydrogel spontaneously and rapidly at the temperature of the human body, and has reversible sol-gel phase transformation characteristic. The temperature-sensitive postoperative adhesion cellulose modifying material is good in biological compatibility, and high in cell adhesion resistance and tissue adhesion resistance, is suitable for adhesion prevention of complicated surgical wounds or wound parts, and has high operation convenience and postoperative adhesion prevention effectiveness.

Description

Cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion and preparation method and application
Technical field
The invention belongs to bio-medical hydrogel material preparing technical field is and in particular to a kind of Thermo-sensitive Prevention of postsurgical adhesion Cellulose modified material and preparation method and application.
Background technology
With a large amount of developments of every surgical operation, postoperative biological tissue adhesion problems become increasingly conspicuous.Adhesion is usually hand Improper connection is there occurs between wound location that postoperative wound, infection or other factors are led to and surrounding tissue or organ And the anomaly sxtructure being formed.Post-operation adhesion not only affects surgical effect, can also result in serious postoperative complications, such as small intestine stalk Resistance, women's pelvic adhesion etc., make operative failure.Therefore, find effective method prevention of postoperative adhesion biomedical engineering always The important topic in field.
So far the most widely used means of preventing adhesion are implantation physics barrier materials, by separating wounded tissue and surrounding Organ is thus prevent adhesion.Conventional adhesion-reducing barrier mainly has following three classes:One is solid state film material, such as patent Disclosed in a kind of post-operation adhesion preventing membrane material, patent CN104436317A disclosed in CN103044700A, a kind of post-operation adhesion preventing is high Molecular film etc., such material is not because of advance comprising, easy to operate and be difficult to be applied to the wounds of some complexity in surgical procedure Position, its application is restricted;Two classes are water liquid class materials, and as disclosed in patent CN103271939A, a kind of operation is with antiseized Even flushing liquor, this kind of material has good mobility, injectable or the wound location being coated on complexity, but easy loss, resistance Fall short of every the time, effect limited;Three is Hydrogels material, has mobility under certain condition, also injectable or coating In complicated surgical wound surface or wound location, and the obstruct time is relatively long, and what such as the scholar such as Yeo reported can in-situ cross-linked pair of group Part hydrogel (Biomaterials, 2006,27:4698-4705;Biomaterials,2007,28:3418-3426), but its The chemical cross-linking agent of certain toxicity is employed during preparation.Consider from the mechanism of action preventing postoperative tissue adhesion, by relevant physics Obstruct means are successfully applied to Prevention of postsurgical adhesion, and adhesion-reducing barrier should have good anti-protein non-specific adsorption Or cell adherence performance, but above-mentioned physical barrier material does not generally have this respect performance, causes its application effect not ideal enough.
Content of the invention
In order to overcome the shortcoming of prior art with not enough, the primary and foremost purpose of the present invention is to provide a kind of Thermo-sensitive to prevent postoperative The preparation method of the cellulose modified material of adhesion, that is, with there is temperature sensitive and excellent biocompatibility methylcellulose as main chain, With there is Anti cell adhesion or protein non-specific adsorption property sulphonic acid betaine type amphoteric ion polymer for side chain structure Build the cellulose modified material of Prevention of postsurgical adhesion.
Another object of the present invention is to providing the Thermo-sensitive Prevention of postsurgical adhesion cellulose obtaining based on above-mentioned preparation method Material modified.This cellulose modified material does not use the chemical cross-linking agent of genotoxic potential, and its aqueous solution is to be easy at room temperature Injection or coating viscous liquid, under human body temperature then can spontaneous quick formation hydrogel, there is reversible sol-gel phase Conversion characteristic.
It is still another object of the present invention to provide the cellulose modified material of above-mentioned Thermo-sensitive Prevention of postsurgical adhesion is as anti-caecum The purposes of post-operation adhesion material.
The purpose of the present invention is achieved through the following technical solutions:
A kind of preparation method of the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion, specifically includes following steps:
(1) in methylated cellulose aqueous solution, zwitterionic monomer methacryloylethyl sulfobetaines, initiation are added Agent and N, N, N', N'- tetramethylethylenediamine, carry out free yl graft polymerization reaction under nitrogen or argon, reaction completes Dialysis freeze-drying afterwards, obtains methylcellulose grafting methacryloylethyl sulfobetaines zwitterionic monomer copolymerization Thing;
(2) the methylcellulose grafting methacryloylethyl sulfobetaines zwitterionic monomer that step (1) is obtained Copolymer is dissolved in buffer solution, is configured to aqueous copolymers solution, the cellulose modified material of as described Thermo-sensitive Prevention of postsurgical adhesion.
Methylated cellulose aqueous solution described in step (1), is that methylcellulose is added to 70~80 DEG C of hot distilled waters In, then it is extremely fully transparent and prepared to be placed in continuation stirring in ice-water bath.Described methylated cellulose aqueous solution mass fraction is preferably 1.0%~4.0%.
Methacryloylethyl sulfobetaines described in step (1) and the Methyl cellulose in methylated cellulose aqueous solution The mass ratio of element is (1:2)~(1:8).
Initiator described in step (1), N, N, N', N'- tetramethylethylenediamine and methacryloylethyl sulfobetaines The mass ratio of alkali is (1:1:20)~(1:1:10), more preferably 1:1:10.
The condition of the free yl graft polymerization reaction described in step (1) is preferably 25~45 DEG C, time 12~24h.
Initiator described in step (1) is at least one in ammonium persulfate, potassium sulfate and sodium peroxydisulfate, preferably Ammonium sulfate.
Buffer solution described in step (2) is disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution (pH=7.4), acetic acid-acetic acid Sodium buffer solution (pH=6.8), citric acid-sodium citrate buffer solution (pH=7.2) or citric acid-sodium hydroxide-hydrochloride buffer (pH=7.0).
Aqueous copolymers solution described in step (2), is that methylcellulose is grafted methacryloylethyl sulfobetaines Alkali zwitterionic monomer copolymer adds in buffer solution, then is placed in ice-water bath and stirs to being completely dissolved, and puts in 4 DEG C of refrigerators Put overnight and be obtained.The mass fraction of described aqueous copolymers solution is preferably 10%~20%.
Present invention also offers a kind of Thermo-sensitive Prevention of postsurgical adhesion cellulose being prepared by above-mentioned preparation method is changed Property material.
Present invention also offers the cellulose modified material of above-mentioned Thermo-sensitive Prevention of postsurgical adhesion prevent adhesion as internal wound deposited The application process of material, for example can be used as anti-caecum post-operation adhesion material.The described cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion Material can be used alone, and uses after also can adding other external used medicines.
The described cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion is used alone, and refers to directly be grafted methylcellulose Methacryloylethyl sulfobetaines zwitterionic monomer aqueous copolymers solution is injected in internal wound, under body temperature Form hydrogel.
The described cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion uses after adding other external used medicines, and its step is such as Under:
(A) weigh 1-100 milligram medicine (as ampicillin), add methylcellulose grafting methacryloylethyl In sulfobetaines zwitterionic monomer aqueous copolymers solution, it is placed in after low temperature stirring and dissolving in 4 DEG C of refrigerators and stands overnight, be obtained The aqueous copolymers solution of embedding medicinal, is the viscous liquid being easy to inject under room temperature;
(B) aqueous copolymers solution of step (A) gained embedding medicinal is injected in internal wound, gets final product shape under body temperature Become the hydrogel of carrying medicament.
Compared with prior art, the present invention has advantages below and beneficial effect:
(1) primary raw material that the present invention adopts is abundance and the methyl fibre with biological safety and biological degradability Dimension element, low price.
(2) present invention does not use chemical cross-linking agent, only leans on the temperature sensitive peculiar property of methylcellulose segment in aqueous It is physical crosslinking, safety non-toxic.
(3) gelling temperature of the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion of gained of the present invention is 30~35 DEG C, Under room temperature be easy to inject or coat viscous liquid, under human body temperature then can spontaneous quick formation hydrogel, have reversible Sol-gel phase in version characteristic.
(4) the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion of gained of the present invention can be used as internal wound prevent adhesion deposited Material, has certain application prospect in biomedical materials field.
(5) present invention operation is simple, and low for equipment requirements, applicability is wide.
Brief description
Fig. 1 is the process chart preparing the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion.
Fig. 2 is the dynamic temperature of the Thermo-sensitive Prevention of postsurgical adhesion cellulose modified material hydrogel sample that embodiment 2 is obtained Scanning curve (G':Storage modulus, G ":Loss modulus):△ represents methylcellulose grafting methacryloylethyl sulfobetaines The G' temperature curve of alkali zwitterionic monomer copolymer aquagel;Represents methylcellulose grafting methacryloylethyl sulphur The G of base beet alkali ampholytic ion monomer copolymer aquagel " temperature curve.
Fig. 3 is the cell adherence growing state microphotograph of the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion.
Fig. 4 is the cellulose modified materials application of Thermo-sensitive Prevention of postsurgical adhesion in the photo of rat cecal wound model.
Specific embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention do not limit In this.Unless stated otherwise, involved reagent in embodiment, method are reagent commonly used in the art and method.
Embodiment 1
(1) weigh the distilled water that the methylcellulose (MC) that 1.0 grams of viscosity are 15cP is added to 80 DEG C of 50mL, then will Flask is placed in continuation stirring in ice-water bath makes it be completely dissolved, transparent liquid.Weigh 0.5 gram of methacryloylethyl sulphur again Base glycine betaine (DMAPS) is added to flask and continues to stir, and is passed through nitrogen protection.It is subsequently adding 50 milligrams of ammonium persulfates (APS) initiator and 65 microlitres of N are made, N, N', N'- tetramethylethylenediamine (TEMED, density 0.775g/mL, similarly hereinafter) make to promote Agent, reacts 24 hours under the conditions of 25 DEG C in a nitrogen atmosphere.After having reacted, reactant liquor is transferred completely into molecular cut off is In 8000 bag filter, deionized water is dialysed 3 days, obtains methylcellulose grafting methacryloylethyl sulfo group sweet after being lyophilized Dish alkali zwitterionic monomer copolymer.
(2) weigh the methylcellulose grafting methacryloylethyl sulfobetaines amphion that 1 gram of step (1) is obtained Monomer copolymer, and add the disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution of 5 milliliters of pH=7.4, it is placed in ice-water bath and constantly stir Mix and so that it is dissolved.4 DEG C of refrigerators stand overnight after so that bubble is escaped, obtain the aqueous copolymers solution that mass fraction is 20%, It is placed in preserving at 4 DEG C.
(3) aqueous copolymers solution is heated to 37 DEG C, that is, is changed into immobilising gel, obtain methylcellulose grafting Methacryloylethyl sulfobetaines zwitterionic monomer copolymer aquagel sample.
Embodiment 2
(1) weigh the distilled water that the methylcellulose (MC) that 1.2 grams of viscosity are 15cP is added to 80 DEG C of 50mL, then will Flask is placed in continuation stirring in ice-water bath makes it be completely dissolved, transparent liquid.Weigh 0.3 gram of methacryloylethyl sulphur again Base glycine betaine (DMAPS) is added to flask and continues to stir, and is passed through nitrogen protection.It is subsequently adding 30 milligrams of ammonium persulfates (APS) initiator and 40 microlitres of N are made, N, N', N'- tetramethylethylenediamine (TEMED) makees accelerator, 45 DEG C in a nitrogen atmosphere Under the conditions of react 12 hours.After having reacted, reactant liquor is transferred completely in the bag filter that molecular cut off is 8000, spend from Sub- water is dialysed 3 days, obtains methylcellulose grafting methacryloylethyl sulfobetaines zwitterionic monomer copolymerization after being lyophilized Thing.
(2) weigh the methylcellulose grafting methacryloylethyl sulfobetaines amphion that 1 gram of step (1) is obtained Monomer copolymer, and add the disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution of 10 milliliters of pH=7.4, it is placed in ice-water bath constantly Stirring makes it dissolve.4 DEG C of refrigerators stand overnight after so that bubble is escaped, obtain the copolymer that mass fraction is 10% water-soluble Liquid, is placed in preserving at 4 DEG C.
(3) aqueous copolymers solution is heated to 37 DEG C, that is, is changed into immobilising gel, obtain methylcellulose grafting Methacryloylethyl sulfobetaines zwitterionic monomer copolymer aquagel sample.
(4) gelling temperature of copolymer aquagel is surveyed using the senior rotational rheometer of ARES/RFS type (TA, USA) Fixed, fixture is 25 millimeters of plate jig, at 20 DEG C by the aqueous copolymers solution uniform application of 1mL 10% to flat board on, stand It is engraved in and measure under dynamic temperature sweep pattern.Measuring condition:Frequency (Frequency) is 1rad/s, deformation (Strain) For 1%, scan temperature range and be 25~40 DEG C, heating rate is 1 DEG C/min, the spacing (Gap) of plate jig is actual by experiment Adjustment is defined, and this experiment typically takes 0.8 millimeter.
Result as shown in Fig. 2 when storage modulus G' be more than loss modulus G " when, sample has formed gel state, now Temperature is then the gelling temperature of sample, and its value is 33 DEG C.
Embodiment 3
(1) reference implementation example 2 makes the methylcellulose grafting methacryloylethyl sulfo group that mass fraction is 10% Beet alkali ampholytic ion monomer aqueous copolymers solution, is placed in preserving at 4 DEG C.
(2) weigh the methylcellulose that 1 gram of viscosity is 15cP and add the disodium hydrogen phosphate-phosphoric acid of 10 milliliters of pH=7.4 Sodium dihydrogen buffer solution, being placed in ice-water bath to be stirred continuously makes it dissolve.4 DEG C of refrigerators stand overnight after so that bubble is escaped, obtain The methylated cellulose aqueous solution being 10% to mass fraction, is placed in preserving at 4 DEG C.
(3) methylated cellulose aqueous solution and methylcellulose is used to be grafted methacryloylethyl sulfobetaines both sexes respectively The half area of ion monomer aqueous copolymers solution uniform fold Tissue Culture Plate, the other half area of culture plate is used as blank Comparison.Culture plate is placed in 37 DEG C of cell culture incubator, so that gel sample is sufficiently formed.Will be equal for people's nasopharyngeal epithelial cells NP69 Even kind, on culture plate, is placed in overnight incubation in 37 DEG C of cell culture incubators containing 5%CO2, then uses tetrazolium bromide (MTT) to thin Born of the same parents are dyeed, and the adhesion growing state with microscope observation of cell.
(4) result is as shown in Figure 3 it is seen that there is more cell adherence to grow on methyl cellulose hydrogel sample surfaces, And on methylcellulose grafting methacryloylethyl sulfobetaines zwitterionic monomer copolymer aquagel sample surfaces Cell number is less, illustrates that copolymer aquagel has the property of Anti cell adhesion growth.
Embodiment 4
(1) reference implementation example 2 makes the methylcellulose grafting methacryloylethyl sulfo group that mass fraction is 10% Beet alkali ampholytic ion monomer aqueous copolymers solution, is placed in preserving at 4 DEG C.
(2) weigh the methylcellulose that 1 gram of viscosity is 15cP and add the disodium hydrogen phosphate-phosphoric acid of 10 milliliters of pH=7.4 Sodium dihydrogen buffer solution, being placed in ice-water bath to be stirred continuously makes it dissolve.4 DEG C of refrigerators stand overnight after so that bubble is escaped, obtain The methylated cellulose aqueous solution being 10% to mass fraction, is placed in preserving at 4 DEG C.
(3) weigh 100 milligrams of ampicillins, be added to the aqueous copolymers solution that step (1) is obtained, low temperature stirs to complete CL, is obtained the aqueous copolymers solution of embedding ampicillin, is placed in preserving at 4 DEG C.
(4) weigh 100 milligrams of ampicillins, be added to the methylated cellulose aqueous solution that step (2) is obtained, low temperature stirs To being completely dissolved, the methylated cellulose aqueous solution of embedding ampicillin is obtained, is placed in preserving at 4 DEG C.
(5) with 3% amobarbital (30 mg/kg), intraperitoneal injection of anesthesia is carried out to 200~250 grams of cleaning grade SD rats Afterwards, cut off Mao Bingyong 75% alcohol disinfecting of belly.On super-clean bench, after SD rat laparotomy, caecum is scratched together about 0.5 centimetre of wound, then injection loads the methylated cellulose aqueous solution of ampicillin and loads ampicillin respectively Methylcellulose grafting methacryloylethyl sulfobetaines zwitterionic monomer aqueous copolymers solution covers wound.Standing 5 Minute is formed after gel after it, caecum is resetted, abdominal incision operation suture thread is sewed on, and continues to feed.
(6) after performing the operation one week, SD rat is put to death, again cut abdominal incision open, observe the adhesion feelings of former caecum wound Condition.Result is as shown in Figure 4 it is seen that the adhesion between caecum and caecum using the rat of methyl cellulose hydrogel, and uses Methylcellulose is grafted the former caecum of the rat of methacryloylethyl sulfobetaines zwitterionic monomer copolymer aquagel Wound healing is normal.
Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention are not subject to above-described embodiment Limit, other any Spirit Essences without departing from the present invention and the change made under principle, modification, replacement, combine, simplify, All should be equivalent substitute mode, be included within protection scope of the present invention.

Claims (10)

1. a kind of preparation method of the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion is it is characterised in that comprise the steps:
(1) in methylated cellulose aqueous solution, add zwitterionic monomer methacryloylethyl sulfobetaines, initiator and N, N, N', N'- tetramethylethylenediamine, carries out free yl graft polymerization reaction under nitrogen or argon, after the completion of reaction thoroughly Analysis freeze-drying, obtain methylcellulose grafting methacryloylethyl sulfobetaines zwitterionic monomer copolymer;
(2) the methylcellulose grafting methacryloylethyl sulfobetaines zwitterionic monomer copolymerization that step (1) is obtained Thing is dissolved in buffer solution, is configured to aqueous copolymers solution.
2. the preparation method of the cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion according to claim 1, its feature It is, the methylcellulose in the methacryloylethyl sulfobetaines described in step (1) and methylated cellulose aqueous solution Mass ratio be (1:2)~(1:8).
3. the preparation method of the cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion according to claim 1, its feature It is, the initiator described in step (1), N, N, N', N'- tetramethylethylenediamine and methacryloylethyl sulfobetaines Mass ratio is (1:1:20)~(1:1:10).
4. the preparation method of the cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion according to claim 1, its feature It is, the condition of the free yl graft polymerization reaction described in step (1) is 25~45 DEG C, time 12~24h.
5. the preparation method of the cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion according to claim 1, its feature It is, the methylated cellulose aqueous solution described in step (1), be that methylcellulose is added in 70~80 DEG C of hot distilled waters, It is placed in continuation stirring in ice-water bath more extremely fully transparent and prepared.
6. the preparation method of the cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion according to claim 1, its feature It is, the initiator described in step (1) is at least one in ammonium persulfate, potassium sulfate and sodium peroxydisulfate.
7. the preparation method of the cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion according to claim 1, its feature It is, the buffer solution described in step (2) is disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution, acetic acid-sodium acetate buffer solution, lemon Lemon acid-sodium citrate buffer solution or citric acid-sodium hydroxide-hydrochloride buffer.
8. the preparation method of the cellulose modified material of a kind of Thermo-sensitive Prevention of postsurgical adhesion according to claim 1, its feature It is, the aqueous copolymers solution described in step (2), be that methylcellulose is grafted methacryloylethyl sulfobetaines two Property ion monomer copolymer add in buffer solution, then be placed in ice-water bath and stir to being completely dissolved, and placed in 4 DEG C of refrigerators Night and be obtained.
9. a kind of cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion is it is characterised in that it is by any one of claim 1 to 8 institute A kind of preparation method of the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion stated prepares.
10. the cellulose modified material of Thermo-sensitive Prevention of postsurgical adhesion described in claim 9 prevents adhesion dressing as internal wound Application.
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CN107537059A (en) * 2017-10-01 2018-01-05 刘云晖 A kind of two-component solubility amphion aerogel dressing and preparation method thereof
CN107537059B (en) * 2017-10-01 2020-06-05 山东煜和堂药业有限公司 Two-component soluble amphoteric ion hydrogel dressing and preparation method thereof
CN108752530A (en) * 2018-05-09 2018-11-06 同济大学 It can the temperature-sensitive hydrogel materials of load cells, temperature-sensitive hydrogel and the preparation method and application thereof
CN109826015A (en) * 2019-01-30 2019-05-31 广西大学 Temperature sensitive/pH the double-bang firecracker of one kind answers intelligent nano fibrous material and its preparation method and application
CN109826015B (en) * 2019-01-30 2021-03-26 广西大学 temperature-sensitive/pH dual-response intelligent nanofiber material and preparation method and application thereof
CN109966539A (en) * 2019-04-11 2019-07-05 中原工学院 A kind of preparation method of low adherency wound dressing
CN110384831A (en) * 2019-06-30 2019-10-29 天津大学 Preparation method for the amphoteric ion hydrogel and crosslinking agent of post-operation adhesion preventing, polymer
CN110384831B (en) * 2019-06-30 2021-10-08 天津大学 Preparation method of zwitterionic hydrogel for postoperative adhesion prevention, cross-linking agent and polymer
CN114835826A (en) * 2022-04-22 2022-08-02 深圳华源再生医学有限公司 Zwitterionic cellulose and preparation method and application thereof
CN114835826B (en) * 2022-04-22 2023-08-22 深圳华源再生医学有限公司 Zwitterionic cellulose and preparation method and application thereof
CN115322397A (en) * 2022-09-23 2022-11-11 福州大学 Zwitterionic hydrogel for preventing postoperative abdominal adhesion and preparation method thereof
CN115322397B (en) * 2022-09-23 2024-04-30 福州大学 Zwitterionic hydrogel for preventing postoperative abdominal adhesion and preparation method thereof

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