A kind of post-operation adhesion preventing hydrogel and preparation method thereof
Technical field
The invention belongs to biomedical material technologies, are related to a kind of with post-operation adhesion preventing, antibacterial, more hemostasis, wound
Medical aquogel of effect and preparation method thereof.
Background technology
Postoperative intestinal adhesion is that had one of important difficult medical problem urgently to be resolved hurrily both at home and abroad since history of operation.It is opened in surgical field
In the operation of exhibition, the overwhelming majority is directed to the problem of preventing adhesion between tissue, and adhesion generation can not only bring pain to patient
Operation expense bitter and that great number need to be faced, therefore it is very urgent to develop preventing adhesions material.Under normal circumstances, connective tissue
Fiber band be that will not stick together, but after underwent operative with adjacent organ or tissue, because operation wound, wound ischaemic,
Foreign matter exists, bleeding and exposure wound surface and bacterium infection and there is connective fiber band and adjacent tissue or organ is sticked to
Anomaly sxtructure together and in the common clinical picture-adhesion of surgical field.Postoperative intestinal adhesion can cause it is serious simultaneously
Disease is sent out, such as abdomen, pelvic cavity can cause adhesive ileus, recurrent nerve injury be caused after thyroid operation and because of pelvic cavity
Female sterility caused by tissue adhesion.Wherein, being the patient of abdominal operation, there are about 93% to have adhesion, and undergoes
The incidence for crossing patient's adhesion of gynecological surgery is up to 97%(40% is as caused by adhesion in infertile women).Therefore, how to have
Effect prevention of postoperative adhesion is come to reduce the incidence of clinical complication be important topic urgently to be resolved hurrily in clinical treatment.
Clinically mainly there is gel-like and two kinds polylactic acid-based using more Prevention of postsurgical adhesion material at present:Gel-like
(Sodium Hyaluronate and chitosan gel rubber)In vivo can be biodegradable, but degradation rate is too fast, internal retention time it is too short and
And gel is easily lost in so that preventing adhesiving effect is not good enough;It is polylactic acid-based(L-lactic acid, racemic polylactic acid etc.)It is at present in life
Object engineering in medicine applies most materials, at the same be also by one of several biomaterials few in number of U.S. FDA certification,
But it can generate acid degradation products in degradation process, on the one hand acidic materials play autocatalysis, the drop for accelerating parent
Solution, reduces internal retention time, reduces preventing adhesiving effect, on the other hand a large amount of acid product accumulations, and there may be non-
Infective inflammation causes certain stimulation to tissue and organ.Sodium alginate has good biocompatibility, biodegradable
The biological properties such as property, hemostatic, it is less currently as the report of adherence preventing material.Ideal adherence preventing material should have good
Biocompatibility, suitable tissue adherence(It is not required to suture), wound surface can be completely covered and retained in vivo with enough
Time;The absorption that can degrade is drawn off without second operation;Play the role of effectivelying prevent Adhesion formation, and can not shadow
Ring the normal healing processes of wound;Hemostasis, antibacterial are taken into account simultaneously, promote effect more and have certain mechanical strength and toughness, with
Convenient in operation by material be implanted into etc..
In having patent, CN 103224679A disclose a kind of Chitosan polyacrylamide hydrogel base material, by
The solution compositions such as acrylamide, methylene diacrylamide, ammonium persulfate, tetramethylethylenediamine, chitosan, obtain different hardness
Hydrogel and with free of toxic effects, reduces the complexity of research cyto-mechanics.CN 104558420A disclose a kind of temperature
With pH sensibility carboxymethyl chitosan hydrogels, respectively with ammonium persulfate, N, N, N ', N '-tetramethylethylenediamine and N, N '-methylene
Base bisacrylamide is initiator, accelerating agent and crosslinking agent, is made by cross-linking reaction so that its biocompatibility is carried
Height expands its application range.CN 103396562A disclose a kind of preparation based on sodium alginate-acrylamide gel
Method, using acrylamide monomer, methylene diacrylamide as crosslinking agent, ammonium persulfate and N, N, N ', N '-tetramethylethylenediamine is
Catalyst obtains the Sodium Alginate Hydrogel Films of high intensity, high tenacity.Alginate-polyacrylamide hydrogel prepared by Li et al.
High intensity and toughness can be provided simultaneously with, using acrylamide, N, N '-methylene-bisacrylamide, CaSO4·2H2O and CaCl2
As crosslinking agent, ammonium persulfate and N, N, N ', N '-tetramethylethylenediamine is hydrogel made from catalyst, is led in bio-medical
Domain has good application prospect.
Invention content
The comprehensive current material of the present invention and the preparation method for improving hydrogel performance, provide a kind of post-operation adhesion preventing water-setting
Chitosan and sodium alginate are carried out the compound hydrogel for preparing high intensity and high tenacity, are expected to by glue and preparation method thereof
For with antibacterial, hemostasis, absorptive tissue diffusate, holding surface of a wound moistening and the post-operation adhesion preventing material for effectively facilitating wound healing
Material.
The purpose of the present invention is what is be achieved through the following technical solutions:
A kind of post-operation adhesion preventing hydrogel, by sodium alginate powder, Chitosan powder, acrylamide monomer, N, N '-methylene
Base bisacrylamide, calcium sulfate, Ammonium Persulfate 98.5 and N, N, N ' N '-tetramethylethylenediamine is prepared, wherein, Chitosan powder
Mass ratio with sodium alginate powder is 8-10:1-3, chitosan and the quality of sodium alginate mixed-powder and acrylamide monomer
Than being 1:The mass ratio of 3-20, N, N '-methylene bisacrylamide acyl and acrylamide monomer be 0.0006-0.0025, calcium sulfate with
The mass ratio of acrylamide monomer is 0.016, and the mass ratio of ammonium persulfate and acrylamide monomer is 0.006-0.03, N, N,
The mass ratio of N ', N '-tetramethylethylenediamine and acrylamide monomer is 0.0025-0.0055.
A kind of preparation method of above-mentioned post-operation adhesion preventing hydrogel, is as follows:
The first step:It is water-soluble that chitosan and sodium alginate mixed-powder are dissolved in 0.5-2w/v% acetic acid at ambient temperature
In liquid, it is made fully to dissolve with magnetic stirrer, obtain the mixed solution of stable homogeneous;
Second step:Acrylamide monomer is added in into the mixed solution that the first step obtains successively, by mixed solution in room temperature
Lower stirring 10-48h is until solution is uniformly dissolved;N is then gradually adding, N '-methylene-bisacrylamide, calcium sulfate are as crosslinking
Agent, Ammonium Persulfate 98.5 and N, N, N ' N '-tetramethylethylenediamine continues to stir 0.5-3h at room temperature, will prepare as catalyst
Good solution stands 0.5-2h deaerations at room temperature;The solution stood is poured into glass mold, stands 6-10h at room temperature
Ensure that it is reacted completely, obtain hydrogel.
Third walks:The hydrogel that second step prepares is fully immersed in the CaCl of a concentration of 0.05-1.5M23- in solution
36h, cation are diffused into hydrogel network structure, are induced chitosan and sodium alginate cross-linking, are prepared high-strength and high-ductility
Composite hydrogel adherence preventing material.
Preferably, a concentration of 0.5-2% of chitosan and sodium alginate mixed-powder in the first step solution(w/w).
Preferably, in the first step chitosan be off-white powder, deacetylation>70%, rank is medical grade, seaweed
Sour sodium is white powder, and rank is medical grade.
Compared with prior art, the beneficial effects of the invention are as follows:
1st, the present invention provides the preparation methods of a kind of high-strength, high tenacity chitosan and sodium alginate composite hydrogel, should
Preparation method is easily operated, and parameter is controllable, and material is easy to get, nontoxic solvent or low toxicity, handles and safe to use;This method is assembled
The advantages of two kinds of natural biologic materials, can be good at the requirement for meeting prevention patient's post-operation adhesion preventing and the shield of medical staff
Manage Treatment need.
2nd, the chitosan and sodium alginate composite hydrogel that prepared by this method have the characteristics that high-strength and high-ductility, compensate for previous
The deficiency of hydrogel, chitosan have broad-spectrum antiseptic, hemostasis, absorb diffusate, more wound and good biocompatibility in itself
And biodegradability, sodium alginate can prepare soluble alginic acid when being contacted with wound exudate by ion exchange
Sodium, while discharge in calcium ion to wound, induced platelet activation can accelerate wound healing.
3rd, the hydrogel softness is easy to and skin attachement, has good flexibility, can effectively prevent surface of a wound adhesion, and
It can be degraded and absorbed, avoid the generation of secondary insult, be expected to become novel post-operation adhesion preventing material.
Specific embodiment
Technical scheme of the present invention is further described with reference to embodiment, however, it is not limited to this, every right
Technical solution of the present invention is modified or replaced equivalently, and without departing from the spirit and scope of technical solution of the present invention, should all be contained
It covers in protection scope of the present invention.
Embodiment 1
(1)It weighs a certain amount of glacial acetic acid respectively with electronic balance, it is water-soluble to be made into the acetic acid that mass fraction is 0.5w/v%
Liquid weighs certain mass CS/SA(9/1)Powder is added in aqueous acetic acid, is configured to the mixed solution of 0.5w/v%, is used magnetic
The stirring of power blender makes it fully dissolve, and obtains the solution of stable homogeneous.
(2)Add in acrylamide monomer into above-mentioned mixed solution successively, by mixed solution be stirred at room temperature 2d until
Solution is uniformly dissolved;Be then gradually adding N, N '-methylene bisacrylamide acyl, calcium sulfate as crosslinking agent, Ammonium Persulfate 98.5 and N, N,
N ' N '-tetramethylethylenediamine continues to stir 1h at room temperature, prepared solution is stood at room temperature as catalyst
0.5-2h deaerations;The solution stood is poured into glass mold, standing a whole night at room temperature ensures that it is reacted completely.Its
In:Chitosan and the mass ratio of sodium alginate mixed-powder and acrylamide monomer are 1:5, N, N '-methylene bisacrylamide acyl are handed over
The mass ratio for joining agent and acrylamide monomer is 0.0006, and the mass ratio of calcium sulfate and acrylamide monomer is 0.016, persulfuric acid
The mass ratio of ammonium and acrylamide monomer is 0.006, N, N, N ', N '-tetramethylethylenediamine and the mass ratio of acrylamide monomer
It is 0.0025.
(3)The hydrogel prepared is fully immersed in the CaCl of a concentration of 0.5M212h in solution, cation diffuse into
Enter in hydrogel network structure, chitosan and sodium alginate cross-linking, the composite hydrogel for producing high-strength and high-ductility is induced to prevent adhesion
Material.
Extension test is carried out to hydrogel obtained, obtains tensile strength as 995.3kPa;Tensile modulus of elasticity 200kPa.
Embodiment 2
(1)It weighs a certain amount of glacial acetic acid respectively with electronic balance, is made into the aqueous acetic acid that mass fraction is 1w/v%,
Weigh certain mass CS/SA(10/2)Powder is added in aqueous acetic acid, is configured to the mixed solution of 1w/v%, is stirred with magnetic force
Mixing device stirring makes it fully dissolve, and obtains the solution of stable homogeneous.
(2)Add in acrylamide monomer into above-mentioned mixed solution successively, by mixed solution be stirred at room temperature 2d until
Solution is uniformly dissolved;Be then gradually adding N, N '-methylene bisacrylamide acyl, calcium sulfate as crosslinking agent, Ammonium Persulfate 98.5 and N, N,
N ' N '-tetramethylethylenediamine continues to stir 1h at room temperature, prepared solution is stood at room temperature as catalyst
0.5-2h deaerations;The solution stood is poured into glass mold, standing a whole night at room temperature ensures that it is reacted completely.Its
In:Chitosan and the mass ratio of sodium alginate mixed-powder and acrylamide monomer are 1:7, N, N '-methylene bisacrylamide acyl are handed over
The mass ratio for joining agent and acrylamide monomer is 0.0010, and the mass ratio of calcium sulfate and acrylamide monomer is 0.016, persulfuric acid
The mass ratio of ammonium and acrylamide monomer is 0.010, N, N, N ', N '-tetramethylethylenediamine and the mass ratio of acrylamide monomer
It is 0.0030.
(3)The hydrogel prepared is fully immersed in the CaCl of a concentration of 0.5M212h in solution, cation diffuse into
Enter in hydrogel network structure, chitosan and sodium alginate cross-linking, the composite hydrogel for producing high-strength and high-ductility is induced to prevent adhesion
Material.
Extension test is carried out to hydrogel obtained, obtains tensile strength as 999.8kPa;Tensile modulus of elasticity 285kPa.
Embodiment 3
(1)It weighs a certain amount of glacial acetic acid respectively with electronic balance, it is water-soluble to be made into the acetic acid that mass fraction is 0.5w/v%
Liquid weighs certain mass CS/SA(9/3)Powder is added in aqueous acetic acid, is configured to the mixed solution of 1w/v%, is used magnetic force
Blender stirring makes it fully dissolve, and obtains the solution of stable homogeneous.
(2)Add in acrylamide monomer into above-mentioned mixed solution successively, by mixed solution be stirred at room temperature 2d until
Solution is uniformly dissolved;Be then gradually adding N, N '-methylene bisacrylamide acyl, calcium sulfate as crosslinking agent, Ammonium Persulfate 98.5 and N, N,
N ' N '-tetramethylethylenediamine continues to stir 1.5h at room temperature, prepared solution is stood at room temperature as catalyst
0.5-2h deaerations;The solution stood is poured into glass mold, standing a whole night at room temperature ensures that it is reacted completely.Shell gathers
Sugar and the mass ratio of sodium alginate mixed-powder and acrylamide monomer are 1:8, N, N '-methylene bisacrylamide acyl crosslinking agent and third
The mass ratio of acrylamide monomer is 0.0012, and the mass ratio of calcium sulfate and acrylamide monomer is 0.016, ammonium persulfate and propylene
The mass ratio of amide monomer is that the mass ratio of 0.012, N, N, N ', N '-tetramethylethylenediamine and acrylamide monomer is 0.0035.
(3)The hydrogel prepared is fully immersed in the CaCl of a concentration of 1M212h in solution, cation diffuse into
In hydrogel network structure, chitosan and sodium alginate cross-linking are induced, the composite hydrogel for producing high-strength and high-ductility prevents adhesion material
Material.
Extension test is carried out to hydrogel obtained, obtains tensile strength as 1166.5kPa;Tensile modulus of elasticity
190.5kPa。
Embodiment 4
(1)It weighs a certain amount of glacial acetic acid respectively with electronic balance, it is water-soluble to be made into the acetic acid that mass fraction is 1.5w/v%
Liquid weighs certain mass CS/SA(10/2)Powder is added in aqueous acetic acid, is configured to the mixed solution of 1.5w/v%, is used magnetic
The stirring of power blender makes it fully dissolve, and obtains the solution of stable homogeneous.
(2)Add in acrylamide monomer into above-mentioned mixed solution successively, by mixed solution be stirred at room temperature 2d until
Solution is uniformly dissolved;Be then gradually adding N, N '-methylene bisacrylamide acyl, calcium sulfate as crosslinking agent, Ammonium Persulfate 98.5 and N, N,
N ' N '-tetramethylethylenediamine continues to stir 1.5h at room temperature, prepared solution is stood at room temperature as catalyst
0.5-2h deaerations;The solution stood is poured into glass mold, standing a whole night at room temperature ensures that it is reacted completely.Its
In:Chitosan and the mass ratio of sodium alginate mixed-powder and acrylamide monomer are 1:10, N, N '-methylene bisacrylamide acyl are handed over
The mass ratio for joining agent and acrylamide monomer is 0.0018, and the mass ratio of calcium sulfate and acrylamide monomer is 0.016, persulfuric acid
The mass ratio of ammonium and acrylamide monomer is 0.018, N, N, N ', N '-tetramethylethylenediamine and the mass ratio of acrylamide monomer
It is 0.0025.
(3)The hydrogel prepared is fully immersed in the CaCl of a concentration of 1M212h in solution, cation diffuse into
In hydrogel network structure, chitosan and sodium alginate cross-linking are induced, the composite hydrogel for producing high-strength and high-ductility prevents adhesion material
Material.
Extension test is carried out to hydrogel obtained, obtains tensile strength as 736.5kPa;Tensile modulus of elasticity
68.5kPa。
Embodiment 5
(1)It weighs a certain amount of glacial acetic acid respectively with electronic balance, is made into the aqueous acetic acid that mass fraction is 2w/v%,
Weigh certain mass CS/SA(8/3)Powder is added in aqueous acetic acid, is configured to the mixed solution of 2w/v%, is stirred with magnetic force
Mixing device stirring makes it fully dissolve, and obtains the solution of stable homogeneous.
(2)Add in acrylamide monomer into above-mentioned mixed solution successively, by mixed solution be stirred at room temperature 2d until
Solution is uniformly dissolved;Be then gradually adding N, N '-methylene bisacrylamide acyl, calcium sulfate as crosslinking agent, Ammonium Persulfate 98.5 and N, N,
N ' N '-tetramethylethylenediamine continues to stir 2h at room temperature, prepared solution is stood at room temperature as catalyst
0.5-2h deaerations;The solution stood is poured into glass mold, standing a whole night at room temperature ensures that it is reacted completely.Its
In:Chitosan and the mass ratio of sodium alginate mixed-powder and acrylamide monomer are 1:10, N, N '-methylene bisacrylamide acyl are handed over
The mass ratio for joining agent and acrylamide monomer is 0.0025, and the mass ratio of calcium sulfate and acrylamide monomer is 0.016, persulfuric acid
The mass ratio of ammonium and acrylamide monomer is 0.025, N, N, N ', N '-tetramethylethylenediamine and the mass ratio of acrylamide monomer
It is 0.0055.
(3)The hydrogel prepared is fully immersed in the CaCl of a concentration of 1M2In solution for 24 hours, cation diffuses into
In hydrogel network structure, chitosan and sodium alginate cross-linking are induced, the composite hydrogel for producing high-strength and high-ductility prevents adhesion material
Material.
Extension test is carried out to hydrogel obtained, obtains tensile strength as 683.7kPa;Tensile modulus of elasticity
78.7kPa。
Chitosan used in above example (CS) be off-white powder, deacetylation>70%, rank is medical grade.Institute
The sodium alginate (SA) stated is white powder, and rank is medical grade.