CN106362221B - A kind of adherence preventing material and preparation method thereof with antibacterial promoting healing function - Google Patents
A kind of adherence preventing material and preparation method thereof with antibacterial promoting healing function Download PDFInfo
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- A61L31/00—Materials 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
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- A61L31/00—Materials 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
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Abstract
The present invention provides a kind of adherence preventing material and preparation method thereof with antibacterial promoting healing function；Adherence preventing material has temperature-responsive, and the transformation of generation that as the temperature rises can be spontaneous from colloidal sol to gel, sol-gel transition temperature is at 5~37 DEG C.The raw material of use is natural Quito sugar xyloglucan and hydroxyl butyl chitosan with good biocompatibility and biodegradability, has the Injectable temperature sensitive gel of controllable sol-gel transition temperature as adherence preventing material by the simple blend preparation of two kinds of polysaccharide solutions.Adherence preventing material prepared by the present invention can be used for the generation of adhesion again after preventing adhesions lysis, while have the function of antibacterial and wound healing.The adherence preventing material preparation method of offer is simple, and parameter is controllable, the convenience of postoperative operation is improved in adhesion again after for preventing adhesions lysis, and can have good potential applicability in clinical practice in conjunction with Minimally Invasive Surgery.
Description
Technical field
The present invention relates to a kind of adherence preventing materials and preparation method thereof with antibacterial promoting healing function, belong to bio-medical
Material Field.
Background technique
Post-operation adhesion is long-term unsolved difficult medical problem in surgical field common problem and clinic
One of.Postoperative adhesion may cause serious complication, such as intestinal obstruction, the ectopic pregnancy, infertile of chronic ache, women
Infertility etc., it is serious to result even in death.It is clinically right in order to weaken or eliminate post-operation adhesion to influence brought by patient
Adhesion release operation is mostly used to be separated in both established adhesions.Adhesiolysis although relieve formed it is viscous
Even, it but will cause new wound again while separating to adhesion organization, thus may result in adhesion release position and glue again
Generation even.Clinical studies show, the postoperative incidence that adhesion again occurs of adhesion release are up to 50%, therefore for adhesion release
The Prevention Research of postoperative adhesion again has very important clinical meaning.
The liquid of existing adherence preventing material, either solid Antiadhesive film or solution or gel-like prevents adhesion material
Material, they are directed to adhesion caused by general surgery trauma, and the Prevention Research of adhesion again postoperative for adhesion release is non-
Often few, relevant patent, which also has no, to be had been reported that.Relative to adhesion caused by general surgical procedures trauma, adhesion release operation pair
Wound caused by adhesion organization is even more serious, and the Forming Mechanism of adhesion again is also more complicated, so, for can be effective
Prevent the physical barriers material of general surgery posterior synechia, in the generation of adhesion again after for preventing adhesions lysis, often
It cannot show good preventing adhesiving effect.
Chitosan is a kind of natural polysaccharide with good biocompatibility and degradability.A large number of studies show that shell is poly-
Sugar can not only inhibit fibroblastic hyperplasia and reduce the generation of collagenous fibres, and can promote endothelial cell growth,
To promote wound healing.Therefore, if postoperative wound can be effectively promoted using chitosan as post-operation adhesion preventing material
Healing and reduce the formation of scar.But since chitosan itself is insoluble in water, so largely limiting answering for it
With.In order to improve the water solubility of chitosan, researcher is modified chitosan by different chemical modification methods, makes respectively
For chitosan derivatives such as water-soluble carboxy methylation, acylation, alkylation and n-trimethyl chitosan chlorides, it is greatly expanded
Its application in every field.Although most of chitosan derivatives all have good water solubility, often do not have
There is temperature-responsive, post-operation adhesion preventing field can not be used for as injection aquagel.If it is possible to keeping chitosan
Improve its water solubility while good biocompatibility and degradability and assign its excellent temperature sensitive performance, then can greatly open up
It is opened up in the application of field of biomedicine.
Infection is to lead to one of factors of post-operation adhesion, and research before mostly has ignored bacterium infection to adhesion shape
At influence be exposed in the wet environment rich in a large amount of peritoneal fluids due to the surface of a wound, greatly mentioned especially for abdominal cavity adhesion
The high probability of bacterium infection, to increase the incidence of post-operation adhesion.Such as diffusate caused by coli-infection
In contain a large amount of fibrin and leucocyte, thus will lead to the formation of close property adhesion.Chitosan is a kind of anti-with wide spectrum
The natural polysaccharide of bacterium performance shows good antibacterial activity for being permitted various bacteria.If can be excellent in imparting chitosan
Its good bacteriostatic activity is kept while Thermo-sensitive, then can play physics when being used as post-operation adhesion preventing material simultaneously
Barrier and anti-infectious synergistic effect prevent art in conjunction with the performance of its wound healing so as to greatly improve it
The effect of posterior synechia and wound healing.
Application No. is 200910052695.7 Chinese patent disclose temperature sensitive chitosan preparation preparation method and its
The application in terms of adhesion is organized after surgery, although the chitosan preparation of this Thermo-sensitive is using rat as the common abdomen of experimental animal
Good preventing adhesiving effect is shown after chamber operation, but according to our result of study, even more serious for wound
The generation of adhesion again can not effectively be prevented after adhesion release operation.Therefore, develop it is novel being capable of effective preventing adhesions pine
Solve the problem that the technical staff that the adherence preventing material that postoperative adhesion again occurs is post-operation adhesion preventing field is faced.
Summary of the invention
The purpose of the present invention is to provide a kind of adherence preventing materials with antibacterial promoting healing function, to solve the prior art
Middle post-operation adhesion preventing material cannot the problem of adhesion occurs again effectively after preventing adhesions lysises.Invention also provides one kind
The preparation method of adherence preventing material with antibacterial promoting healing function, the raw material of use are with good biocompatibility and biology
The natural Quito sugar xyloglucan and hydroxyl butyl chitosan of degradability have the polysaccharide solution of Thermo-sensitive by two kinds in itself
Simple blend preparation has the Injectable temperature sensitive gel of controllable sol-gel transition temperature as adherence preventing material, due to this hair
It is molten that bright prepared adherence preventing material combines the antibacterial of hydroxyl butyl chitosan solution, wound healing ability and xyloglucan
The prevention of postoperative adhesion performance of liquid because can be used for preventing the generation of the postoperative adhesion again of increasingly complex adhesion release, and has simultaneously
There is antibacterial and wound healing function.
The present invention is realized by technical solution below:
A kind of adherence preventing material with antibacterial promoting healing function, the adherence preventing material are by xyloglucan solution and hydroxyl
Butyl shell poly solution is combined.
The adherence preventing material has temperature-responsive, and generation that as the temperature rises can be spontaneous is from colloidal sol to gel
Transformation, sol-gel transition temperature is at 5~37 DEG C.
Specifically, solvent used in xyloglucan solution and hydroxyl butyl shell poly solution is in the post-operation adhesion preventing material
Pure water, physiological saline, buffer solution, cell culture medium, simulated body fluid, animal or human body fluid it is one such or more than one
Mixed solution.
The invention also discloses the preparation methods of the above-mentioned adherence preventing material with antibacterial promoting healing function, including following step
It is rapid:
It (1) is 50,000~5,000,000 by molecular weight under the conditions of 4 DEG C, the wooden Portugal that side chain galactolipin removal efficiency is 35~95% is poly-
Sugar is dissolved in solvent, obtains the xyloglucan solution that mass fraction is 0.1~20%；
It (2) is 50,000~5,000,000 by molecular weight under the conditions of 4 DEG C, the hydroxyl butyl shell that hydroxyl butyl degree of substitution is 0.5~2.0 is poly-
Sugar is dissolved in solvent, obtains the hydroxyl butyl chitosan solution that mass fraction is 0.1~20%；
(3) by the obtained xyloglucan solution of step (1) and the obtained hydroxyl butyl shell of step (2) under the conditions of 4 DEG C
The poly solution progress of 0.5~9.5:9.5~0.5 by volume is compound, and the material that prevents adhesion with antibacterial promoting healing function can be obtained
Material.
Specifically, the obtained xyloglucan solution of step (1) has temperature-responsive, as the temperature rises can be certainly
Transformation of the generation of hair from colloidal sol to gel, sol-gel transition temperature are 5~37 DEG C.
Specifically, the obtained hydroxyl butyl chitosan solution of step (2) has temperature-responsive, as the temperature rises can
Transformation of enough spontaneous generations from colloidal sol to gel, sol-gel transition temperature are 5~37 DEG C.
Compared with prior art, the present invention the advantage is that: (1) present invention is molten by two kinds of polysaccharide with different performance
The simple blend of liquid has obtained having both the adherence preventing material of two kinds of polysaccharide excellent properties, solves post-operation adhesion preventing in the prior art
Material cannot the problem of adhesion occurs again effectively after preventing adhesions lysises (Fig. 8).(2) adherence preventing material prepared by the present invention
Using polysaccharide-based material xyloglucan and hydroxyl butyl chitosan as raw material, the solvent that uses is the green solvents such as water, in preparation process
The use of organic reagent is completely avoided, there is good biocompatibility and biodegradability.(3) prepared by the present invention
Adherence preventing material can rapidly spontaneously form hydrogel (Fig. 1,2,3,4) under physiological temp, avoid chemical cross-linking agent
The generation for using and chemically reacting has good biological safety.(4) the post-operation adhesion preventing material prepared by the present invention contains
Hydroxyl butyl chitosan can play the effect (Fig. 7) of antibacterial (Fig. 6) and wound healing while prevention of postoperative adhesion.
(5) adherence preventing material preparation method provided by the present invention is simple, and parameter is controllable, easy to use, and can be in conjunction with Minimally Invasive Surgery
The prevention of the postoperative adhesion again of adhesion release provides new selection, has good potential applicability in clinical practice.
A kind of adherence preventing material and preparation method thereof with antibacterial promoting healing function disclosed by the invention, adherence preventing material
It is combined by innovation wood dextran solution and hydroxyl butyl shell poly solution, being able to solve adherence preventing material in the prior art cannot have
The problem of adhesion occurs again after effect preventing adhesions lysis.The present invention provides a kind of preventing adhesion with antibacterial promoting healing function
The preparation method of material, the raw material of use are that have the Portugal natural Quito Tang Mu of good biocompatibility and biodegradability poly-
Sugar and hydroxyl butyl chitosan, by the simple blend preparation of two kinds of polysaccharide solutions there is controllable sol-gel transition temperature can
Thermo-sensitive gel is injected as adherence preventing material.Adherence preventing material prepared by the present invention glues again after can be used for preventing adhesions lysis
Generation even, while having the function of antibacterial and wound healing.The adherence preventing material preparation method of offer is simple, and parameter can
Control improves the convenience of postoperative operation in adhesion again after for preventing adhesions lysis, and can have in conjunction with Minimally Invasive Surgery
Good potential applicability in clinical practice.
Detailed description of the invention
Fig. 1 is the storage modulus (G') of the adherence preventing material with antibacterial promoting healing function prepared by the embodiment of the present invention 1
With the temperature scanning rheology result of loss modulus (G ").
Fig. 2 be the embodiment of the present invention 1 prepare the adherence preventing material with antibacterial promoting healing function at 37 DEG C energy storage mould
Measure the time sweep rheology result of (G') and loss modulus (G ").
Fig. 3 is the storage modulus (G') of the adherence preventing material with antibacterial promoting healing function prepared by the embodiment of the present invention 2
With the temperature scanning rheology result of loss modulus (G ").
Fig. 4 be the embodiment of the present invention 2 prepare the adherence preventing material with antibacterial promoting healing function at 37 DEG C energy storage mould
Measure the time sweep rheology result of (G') and loss modulus (G ").
Fig. 5 be the adherence preventing material with antibacterial promoting healing function for preparing of the embodiment of the present invention 3 at different temperatures
Apparent state.
Fig. 6 is the adherence preventing material with antibacterial promoting healing function for preparing of the embodiment of the present invention 3 for Escherichia coli, green
The fungistatic effect of purulence bacillus and staphylococcus aureus.
Fig. 7 is that the adherence preventing material with antibacterial promoting healing function prepared by the embodiment of the present invention 1 and 3 is being used for SD rat
Postoperative 14 days wound healing effects of skin wound model.A: the foundation of the rat skin surface of a wound；B: control group；C, embodiment
The wound healing situation of 1 post-operation adhesion preventing material；D: the wound healing situation of 3 post-operation adhesion preventing material of embodiment.
Fig. 8 is that the adherence preventing material with antibacterial promoting healing function prepared by the embodiment of the present invention 1 is blind in SD rat stomach wall-
Postoperative 7 days preventing adhesiving effect photos in the postoperative secondary damage adhesion model of Intestinal adhesion lysis.A: the control of physiological saline is used
Group sticks together；B: there is no adhesion and wound healings for the animal of adherence preventing material of the use with antibacterial promoting healing function
Well.
Specific embodiment
Embodiment 1
It (1) is 1,000,000 by molecular weight under the conditions of 4 DEG C, the xyloglucan that side chain galactolipin removal efficiency is 41% is dissolved in water
In, obtain the xyloglucan solution that mass fraction is 4%；
It (2) is 400,000 by molecular weight under the conditions of 4 DEG C, the hydroxyl butyl chitosan that hydroxyl butyl degree of substitution is 1.67 is dissolved in water
In, obtain the hydroxyl butyl chitosan solution that mass fraction is 5%；
(3) by the obtained xyloglucan solution of step (1) and the obtained hydroxyl butyl shell of step (2) under the conditions of 4 DEG C
Poly solution 5:5 progress by volume is compound, and the adherence preventing material with antibacterial promoting healing function can be obtained.
To the adherence preventing material with antibacterial promoting healing function that the present embodiment obtains, the rheology result of temperature scanning is aobvious
Show that adherence preventing material that the present embodiment obtains has temperature-responsive, can as the temperature rises spontaneous generation from colloidal sol to
The transformation of gel, sol-gel transition temperature are 26 DEG C；The rheology of time sweep as the result is shown the present embodiment obtain it is anti-sticking
Even gelation can occur in 20 seconds for material at 37 DEG C.
Embodiment 2
The step of this example is with example 1 is essentially identical, the difference is that: by xyloglucan is molten in step (3) in example 1
The volume ratio of liquid and hydroxyl butyl shell poly solution is changed to 3:7 by 5:5, obtains the adherence preventing material with antibacterial promoting healing function.It is right
The adherence preventing material with antibacterial promoting healing function that the present embodiment obtains, the rheology of temperature scanning the present embodiment as the result is shown
Obtained adherence preventing material has temperature-responsive, spontaneous generation can turn from colloidal sol to gel as the temperature rises
Become, sol-gel transition temperature is 28 DEG C；The rheology of the time sweep adherence preventing material that the present embodiment obtains as the result is shown exists
Gelation can occur within 25 seconds at 37 DEG C.
Embodiment 3
The step of this example is with example 1 is essentially identical, the difference is that: by xyloglucan is molten in step (3) in example 1
The volume ratio of liquid and hydroxyl butyl shell poly solution is changed to 0.5:9.5 by 5:5, obtains the material that prevents adhesion with antibacterial promoting healing function
Material.To the adherence preventing material with antibacterial promoting healing function that the present embodiment obtains, bottle anastrophe is the result shows that the present embodiment
There is obtained adherence preventing material reversible " cryosol, high temperature gel " to change behavior；Bactericidal test is the results show that dipping
It crosses and occurs apparent inhibition zone around the filter paper of adherence preventing material manufactured in the present embodiment, illustrate manufactured in the present embodiment
Adherence preventing material has fungistatic effect for Escherichia coli, Pseudomonas aeruginosa and staphylococcus aureus.
Embodiment 4
It (1) is 5,000,000 by molecular weight under the conditions of 4 DEG C, the xyloglucan that side chain galactolipin removal efficiency is 35% is dissolved in water
In, obtain the xyloglucan solution that mass fraction is 1%；
It (2) is 50,000 by molecular weight under the conditions of 4 DEG C, the hydroxyl butyl chitosan that hydroxyl butyl degree of substitution is 2.0 is soluble in water,
Obtain the hydroxyl butyl chitosan solution that mass fraction is 20%；
(3) by the obtained xyloglucan solution of step (1) and the obtained hydroxyl butyl shell of step (2) under the conditions of 4 DEG C
Poly solution 5:5 progress by volume is compound, and the adherence preventing material with antibacterial promoting healing function can be obtained.Embodiment 5
It (1) is 100,000 by molecular weight under the conditions of 4 DEG C, the xyloglucan that side chain galactolipin removal efficiency is 90% is dissolved in water
In, obtain the xyloglucan solution that mass fraction is 10%；
It (2) is 5,000,000 by molecular weight under the conditions of 4 DEG C, the hydroxyl butyl chitosan that hydroxyl butyl degree of substitution is 1.0 is dissolved in water
In, obtain the hydroxyl butyl chitosan solution that mass fraction is 0.5%；
(3) by the obtained xyloglucan solution of step (1) and the obtained hydroxyl butyl shell of step (2) under the conditions of 4 DEG C
Poly solution 7:3 progress by volume is compound, and the adherence preventing material with antibacterial promoting healing function can be obtained.Embodiment 6
It (1) is 50,000 by molecular weight under the conditions of 4 DEG C, the xyloglucan that side chain galactolipin removal efficiency is 50% is soluble in water,
Obtain the xyloglucan solution that mass fraction is 20%；
It (2) is 1,000,000 by molecular weight under the conditions of 4 DEG C, the hydroxyl butyl chitosan that hydroxyl butyl degree of substitution is 0.6 is dissolved in water
In, obtain the hydroxyl butyl chitosan solution that mass fraction is 15%；
(3) by the obtained xyloglucan solution of step (1) and the obtained hydroxyl butyl shell of step (2) under the conditions of 4 DEG C
Poly solution 9:1 progress by volume is compound, and the adherence preventing material with antibacterial promoting healing function can be obtained.Embodiment 7
The present embodiment be by the adherence preventing material prepared by the present invention with antibacterial promoting healing function SD rat skin
It is applied in wound model to investigate its wound healing effect.
Specific method is will to cut respectively after experimental animal SD rat anesthesia, disinfection in the omoplate area of backbone two sides spacing 2cm
The surface of a wound of diameter 2cm is taken, adherence preventing material prepared by 1mL embodiment 1 and 3 is injected to the surface of a wound later, then with aseptic dressing
Flap coverage；The control group surface of a wound is only with Aseptic sterilisation dressing covering.The adherence preventing material of injection in the experimental group surface of a wound every two days, and
It is covered with aseptic dressing, while aseptic dressing is replaced to the control group surface of a wound.Postoperative 14 days relative to control group the results show that make
With the animal of adherence preventing material prepared by embodiment 1 and 3, the surface of a wound has faster healing rate, and wound healing is all right,
And no inflammation reaction occurs.
Embodiment 8
The present embodiment is that the adherence preventing material prepared by the present invention with antibacterial promoting healing function is blind in SD rat stomach wall-
It is applied in the postoperative secondary damage adhesion model of Intestinal adhesion lysis to investigate the pre- preventive effect of its adhesion again postoperative to adhesion release
Fruit.
Specific method is will to open abdomen in white belly line position after experimental animal SD rat anesthesia, disinfection, using eye scissors in abdomen
Wall removes 1 × 2cm2The shallow-layer flesh of size forms bleeding surface；Then hand is used on caecum corresponding with stomach wall surface of a wound surface
Art brushing is wiped until caecum placenta percreta is destroyed to there is apparent petechial hemorrhage；Use 3-0 suture by the mesenterium of caecum later
Suture is fixed at the upper right corner of the stomach wall surface of a wound, to guarantee that the wound face of stomach wall and caecum can come into full contact with and shape between each other
At adhesion.Postoperative one week, secondary abdominal is carried out to animal, is loosened using blunt or sharp instrument to the adhesion of formation, is used
Operation brush rubs the stomach wall surface of a wound after separating until forming bleeding surface again repeatedly；Then the caecum with operation brush after isolation
Wound site gently rubs until intestinal mucosa is destroyed again to there is apparent oozing of blood；Finally have prepared by 1mL embodiment 1
The adherence preventing material of antibacterial promoting healing function is injected to the stomach wall and the caecum surface of a wound of the postoperative secondary damage of adhesion release, complete to gel
Abdomen is closed after all solidstate.
Open abdomen within postoperative 7 days, there is no appointing for the animal of the temperature sensitive injectable post-operation adhesion preventing material prepared using embodiment 1
The adhesion of what form, the stomach wall surface of a wound heal completely, and the surface of a wound any surface finish after healing is smooth, is hardly visible scar and deposits
Impaired caecum also heals well；And it is caused using between the caecum and stomach wall being damaged in the control group of physiological saline
Close adhesion.
Above-described embodiment is the preferable embodiment of the present invention, but the present invention is not limited to the above embodiments.It is not taking off
From on the basis of the spirit and scope of technical solution of the present invention to technical solution of the present invention carry out modification or equivalent replacement,
It should be included within the scope of the present invention.
Claims (5)
1. a kind of adherence preventing material with antibacterial promoting healing function, which is characterized in that the adherence preventing material is gathered by the wooden Portugal
Sugar juice and hydroxyl butyl chitosan solution are combined；The adherence preventing material has temperature-responsive, as the temperature rises
The transformation of generation that can be spontaneous from colloidal sol to gel, sol-gel transition temperature are 5~37 DEG C；Preparation method includes following
Step:
It (1) is 50,000~5,000,000 by molecular weight under the conditions of 4 DEG C, the xyloglucan that side chain galactolipin removal efficiency is 35~95% is molten
In solvent, the xyloglucan solution that mass fraction is 0.1~20% is obtained；
It (2) is 50,000~5,000,000 by molecular weight under the conditions of 4 DEG C, the hydroxyl butyl chitosan that hydroxyl butyl degree of substitution is 0.5~2.0 is molten
In solvent, the hydroxyl butyl chitosan solution that mass fraction is 0.1~20% is obtained；
(3) by the obtained xyloglucan solution of step (1) and the obtained hydroxyl butyl chitosan of step (2) under the conditions of 4 DEG C
The solution progress of 0.5~9.5:9.5~0.5 by volume is compound, obtains the adherence preventing material with antibacterial promoting healing function.
2. adherence preventing material according to claim 1, which is characterized in that the obtained xyloglucan solution tool of step (1)
There is temperature-responsive, the transformation of generation that as the temperature rises can be spontaneous from colloidal sol to gel, sol-gel transition temperature
It is 5~37 DEG C.
3. adherence preventing material according to claim 1, which is characterized in that the obtained hydroxyl butyl chitosan of step (2) is molten
Liquid has temperature-responsive, the transformation of generation that as the temperature rises can be spontaneous from colloidal sol to gel, sol-gel transition
Temperature is 5~37 DEG C.
4. material according to claim 1, which is characterized in that xyloglucan solution and hydroxyl in the post-operation adhesion preventing material
Solvent used in butyl chitosan solution be pure water, physiological saline, buffer solution, cell culture medium, simulated body fluid, animal or
Human body fluid is one such or more than one mixed solution.
5. adherence preventing material according to claim 1, which is characterized in that the adherence preventing material is loosened for preventing adhesions
The generation of postoperative adhesion again, while having the function of antibacterial and wound healing.
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|---|---|---|---|---|
| WO1996002258A1 (en) * | 1994-07-19 | 1996-02-01 | Astra Aktiebolag | Anti-adhesion agent |
| CN101820885A (en) * | 2007-10-03 | 2010-09-01 | Cpn有限公司 | Preparation for wound healing and prevention of bandage adhesion to wound comprising chitosan-dextran |
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2016
- 2016-09-30 CN CN201610870752.2A patent/CN106362221B/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996002258A1 (en) * | 1994-07-19 | 1996-02-01 | Astra Aktiebolag | Anti-adhesion agent |
| CN101820885A (en) * | 2007-10-03 | 2010-09-01 | Cpn有限公司 | Preparation for wound healing and prevention of bandage adhesion to wound comprising chitosan-dextran |
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| 可注射温敏木葡聚糖水凝胶在预防术后粘连中的应用;张二帅等;《2015年全国高分子学术论文报告会》;20151021;第335页全文 |
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