CN107596456A - A kind of biological medicinal membrane with hemostatic function and preparation method thereof - Google Patents
A kind of biological medicinal membrane with hemostatic function and preparation method thereof Download PDFInfo
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- CN107596456A CN107596456A CN201710946276.2A CN201710946276A CN107596456A CN 107596456 A CN107596456 A CN 107596456A CN 201710946276 A CN201710946276 A CN 201710946276A CN 107596456 A CN107596456 A CN 107596456A
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Abstract
The invention discloses a kind of biological medicinal membrane with hemostatic function and preparation method thereof.The biological medicinal membrane with hemostatic function of the present invention, is made up of, the fiber has kernel and shell mechanism, and the kernel is biodegradable polyesters, and the shell is polyglutamic acid fiber parallel connection.The present invention prepares biological medicinal membrane by coaxial electrostatic spinning technology, fiber shell has good hemostatic function and adhesion property, fiber kernel provides physical barriers and mechanical support, so that the biological medicinal membrane has suitable mechanical strength, and hemostasis shell is firmly combined with kernel, it is difficult for drop-off so that the hemostatic function of the biological medicinal membrane is more long-acting.
Description
Technical field
The present invention relates to a kind of biological medicinal membrane, and in particular to a kind of biological medicinal membrane and its preparation with hemostatic function
Method.
Background technology
Surgical site infections tissue adhesion is always a great problem that clinical medicine faces, the whole nation is annual have nearly ten million it is various
The operation case of type, and nearly all operation prevents adhesion and local anti-inflammatory problem between being directed to tissue.In human body abdomen
The tissue adhesion that the surgical site infections such as portion, angiocarpy, backbone, Bones and joints, leg, gynecologic occur not only brings pole to patient
Big pain, and cause huge economic loss.Post-operation adhesion can cause serious complication, and such as belly, pelvic cavity are equal
Adhesive ileus can be caused, recurrent nerve injury is caused after thyroid operation, the adhesion of heart and thorax also needs to try again
Throacotomy and the female sterility caused by pelvic tissue adhesion, and be also when performing the operation again complication substantially increase
Main reason.90% patient has different degrees of adhesion to produce after surgery, and 60% patient needs to take certain anti-
Adhesion measure.
However, generally existing bleeding or oozing phenomenon in surgical procedure, model is used which greatly limits biological medicinal membrane
Enclose, while the probability of increased adhesion, the biological medicinal membrane including INTERCEED and SEPRAFILM all must be abundant
Used after hemostasis, considerably increase the complexity of operating time and operation.Traditional biological medicinal membrane is often directly prepared
One layer of hemostatic function coating, but the coating that stops blooding can be easily separated with substrate, lose haemostatic effect.Research shows that gel has local
Anastalsis, suppress the formation of fibrin beam, advantageously reduce tissue adhesion, but gel poor mechanical property, be unfavorable for grasping
Make.
From above mentioned problem, in order that biological medicinal membrane can use under bleeding, biological medicinal membrane needs full
It is enough lower condition：
(1) there is certain hemostatic function, can be used under bleeding；
(2) there is suitable mechanical strength, it is easy to operation；
(2) self adhesion property is good, if adhesiveness is bad, surgical adhesions film is very restricted in the application, such as abdomen
Between film and intestinal tube, between intestinal tube and intestinal tube, because intestinal tube is in constantly wriggling, biological medicinal membrane easily slides, it is possible to causes
Originally new wound is caused at the lossless position of health.
The content of the invention
In view of the above-mentioned deficiencies in the prior art, it is an object of the present invention to provide a kind of biological medicinal membrane with hemostatic function and
Its preparation method.
To achieve the above object, the technical scheme that the present invention takes is as follows：
A kind of biological medicinal membrane with hemostatic function, it is characterised in that be made up of fiber parallel connection, the fiber has interior
Core and shell mechanism, the kernel are biodegradable polyesters, and the shell is polyglutamic acid.
Bio-medical membrane fiber in above-mentioned technical proposal is made up of the fiber parallel connection with kernel and shell mechanism, shell
For polyglutamic acid, there is good hemostatic function and adhesion property, can be used for preventing adhesion under bleeding；Fiber kernel is
Biodegradable polyesters, there is physical barriers and mechanical support to act on, suitable mechanical strength is provided for biological medicinal membrane；Shell
It is firmly combined with kernel, it is difficult for drop-off.
As the preferred embodiment of the biological medicinal membrane of the present invention with hemostatic function, the biodegradable poly
Ester is Poly(D,L-lactide-co-glycolide (PLGA), PLA or polycaprolactone.
As the preferred embodiment of the biological medicinal membrane of the present invention with hemostatic function, the polyglutamic acid and life
The weight ratio of Biodegradable polyester is 1:5~1:1.
As the preferred embodiment of the biological medicinal membrane of the present invention with hemostatic function, the polyglutamic acid weight is equal
Molecular weight is 900,000~1,500,000.
As the preferred embodiment of the biological medicinal membrane of the present invention with hemostatic function, the biodegradable poly
Ester weight average molecular weight is 50,000~400,000.
The present invention also provides a kind of preparation method of the biological medicinal membrane with hemostatic function, comprises the following steps：
(1) it is polyglutamic acid is soluble in water, polyglutamic acid solution is prepared, as shell spinning solution；
(2) biodegradable polyesters are dissolved in organic solvent, biodegradable polyesters solution are prepared, as kernel spinning
Solution；
(3) coaxial electrostatic spinning technology is used, shell spinning solution and kernel spinning solution are subjected to spinning, obtain electrostatic
Spinning film；
(4) static spinning membrane prepared by vacuum drying step (3), organic solvent and moisture are removed, obtained described with only
The biological medicinal membrane of blood function.
It is described poly- as the preferred embodiment of the preparation method of the biological medicinal membrane of the present invention with hemostatic function
The concentration of polyglutamic acid is 1w/v%~10w/v% in glutamic acid solution.
As the preferred embodiment of the preparation method of the biological medicinal membrane of the present invention with hemostatic function, the life
The concentration of biodegradable polyesters is 8w/v%~20w/v% in Biodegradable polyester liquid.
It is described to have as the preferred embodiment of the preparation method of the biological medicinal membrane of the present invention with hemostatic function
Solvent is dichloromethane, dimethyl sulfoxide (DMSO), trifluoroethanol, chloroform or trifluoroacetic acid.
As the preferred embodiment of the preparation method of the biological medicinal membrane of the present invention with hemostatic function, the step
Suddenly in (3), the condition of coaxial electrostatic spinning is：6~40kV of spinning voltage；Kernel spinning flow velocity is 0.1~10mL/h, and shell is spun
Silk flow velocity is 0.1~5mL/h；Reception device is flat board or cylinder, and reception device is 20cm at syringe needle；Spinning environment temperature
For 25 DEG C.
Compared with prior art, beneficial effects of the present invention are：
The biological medicinal membrane fiber shell prepared by coaxial electrostatic spinning technology is polyglutamic acid, has good hemostasis
Function, it can be used for preventing adhesion under bleeding；Fiber kernel is biodegradable polyesters, has physical barriers and mechanics branch
Support is acted on, and suitable mechanical strength is provided for biological medicinal membrane.
Biological medicinal membrane of the present invention has core shell structure, compared with the multilayer of existing biological medicinal membrane is directly superimposed, hemostasis
Coated shell combined with kernel it is more firm, hemostatic function coating keep effect time it is more long-acting.
Polyglutamic acid outer shell has good adhesion property, can effectively solve the problem that biological medicinal membrane in the application because of intestinal tube
The problem of causing biological medicinal membrane to slide Deng continuous wriggle.
Brief description of the drawings
Fig. 1 is polyglutamic acid/PLGA electrospun fibers core shell structure scanning electron microscope diagrams in embodiment 1.
Embodiment
For the object, technical solutions and advantages of the present invention are better described, below in conjunction with the drawings and specific embodiments pair
The present invention further illustrates.It will be appreciated by those skilled in the art that specific embodiment described herein is only explaining this hair
It is bright, it is not intended to limit the present invention.
Embodiment 1
The present invention has a kind of embodiment of the biological medicinal membrane of hemostatic function, has hemostatic function described in the present embodiment
Biological medicinal membrane.
The preparation method of the biological medicinal membrane with hemostatic function is described in the present embodiment：
(1) polyglutamic acid (molecular weight 900,000) is dissolved in deionized water, stirred, preparing polyglutamic acid percentage by weight is
1w/v% outer shell spinning solution；
(2) PLGA (molecular weight is 400,000) is dissolved in dichloromethane, stirs, prepare the kernel that PLGA concentration is 8w/v%
Layer spinning solution；
(3) coaxial electrostatic spinning technology is used, shell spinning solution and kernel spinning solution are subjected to spinning, are prepared
The weight ratio of static spinning membrane, wherein polyglutamic acid and PLGA is 1:5；Wherein, spinning voltage 6kV, kernel spinning flow velocity are
0.1mL/h, shell spinning flow velocity are 0.1mL/h, and reception device is flat board, and reception device is 20cm at syringe needle, spinning ring
Border temperature is 25 DEG C.
(4) static spinning membrane prepared by vacuum drying step (3), dichloromethane solvent and moisture is removed, obtains the tool
There is hemostatic function biological medicinal membrane.
Embodiment 2
The present invention has a kind of embodiment of the biological medicinal membrane of hemostatic function, has hemostatic function described in the present embodiment
Biological medicinal membrane.
The preparation method of the biological medicinal membrane with hemostatic function is described in the present embodiment：
(1) polyglutamic acid (molecular weight 1,000,000) is dissolved in deionized water, stirred, it is 4w/ to prepare polyglutamic acid concentration
V% outer spinning solution；
(2) PLGA (molecular weight is 100,000) is dissolved in dimethyl sulfoxide (DMSO), stirred, it is 10w/v%'s to prepare PLGA concentration
Kernel spinning solution；
(3) coaxial electrostatic spinning technology is used, shell spinning solution and kernel spinning solution are subjected to spinning, are prepared
The weight ratio of static spinning membrane, wherein polyglutamic acid and PLGA is 1:1；Wherein, spinning voltage 10kV, kernel spinning flow velocity are
2mL/h, shell spinning flow velocity are 0.5mL/h, and reception device is flat board, and reception device is 20cm at syringe needle, spinning environment
Temperature is 25 DEG C.
(4) static spinning membrane for preparing step (3) is dried in vacuo 2 days, is removed dimethyl sulfoxide solvent and moisture, is obtained
It is described that there is hemostatic function biological medicinal membrane.
Embodiment 3
The present invention has a kind of embodiment of the biological medicinal membrane of hemostatic function, has hemostatic function described in the present embodiment
Biological medicinal membrane.
The preparation method of the biological medicinal membrane with hemostatic function is described in the present embodiment：
(1) polyglutamic acid (molecular weight 1,200,000) is dissolved in deionized water, be dispersed with stirring, preparing polyglutamic acid concentration is
6w/v% shell spinning solution；
(2) PLGA (molecular weight is 50,000) is dissolved in trifluoroethanol, stirs, prepare the kernel that PLGA concentration is 15w/v%
Spinning solution；
(3) coaxial electrostatic spinning technology is used, shell spinning solution and kernel spinning solution are subjected to spinning, are prepared
The weight ratio of static spinning membrane, wherein polyglutamic acid and PLGA is 1:2；Wherein, spinning voltage 20kV, kernel spinning flow velocity are
4mL/h, shell spinning flow velocity are 1mL/h, and reception device is cylinder, and reception device is 20cm at syringe needle, spinning environment temperature
Spend for 25 DEG C.
(4) static spinning membrane prepared by vacuum drying step (3), trifluoroethanol solvent and moisture is removed, obtains the tool
There is hemostatic function biological medicinal membrane.
Embodiment 4
The present invention has a kind of embodiment of the biological medicinal membrane of hemostatic function, has hemostatic function described in the present embodiment
Biological medicinal membrane.
The preparation method of the biological medicinal membrane with hemostatic function is described in the present embodiment：
(1) polyglutamic acid (molecular weight 1,000,000) is dissolved in deionized water, stirred, it is 8w/ to prepare polyglutamic acid concentration
V% shell spinning solution；
(2) PLA (molecular weight is 300,000) is dissolved in chloroform, stirred, it is the interior of 18w/v% to prepare PLA concentration
Core spinning solution；
(3) coaxial electrostatic spinning technology is used, shell spinning solution and kernel spinning solution are subjected to spinning, are prepared
The weight ratio of static spinning membrane, wherein polyglutamic acid and PLA is 1:5；Wherein, spinning voltage 30kV, kernel spinning flow velocity are
8mL/h, shell spinning flow velocity are 2mL/h, and reception device is flat board, and reception device is 20cm at syringe needle, spinning environment temperature
Spend for 25 DEG C.
(4) static spinning membrane prepared by vacuum drying step (3), chloroform solvent and moisture are removed, obtained described with only
Blood functional biological medical films.
Embodiment 5
The present invention has a kind of embodiment of the biological medicinal membrane of hemostatic function, has hemostatic function described in the present embodiment
Biological medicinal membrane.
The preparation method of the biological medicinal membrane with hemostatic function is described in the present embodiment：
(1) polyglutamic acid (molecular weight 1,500,000) is dissolved in deionized water, stirred, it is 10w/ to prepare polyglutamic acid concentration
V% shell spinning solution；
(2) polycaprolactone (molecular weight is 200,000) is dissolved in trifluoroacetic acid, stirred, it is 20w/ to prepare polycaprolactone concentration
V% kernel spinning solution；
(3) coaxial electrostatic spinning technology is used, shell spinning solution and kernel spinning solution are subjected to spinning, are prepared
The weight ratio of static spinning membrane, wherein polyglutamic acid and polycaprolactone is 1:3；Wherein, spinning voltage 40kV, kernel spinning flow velocity
For 10mL/h, shell spinning flow velocity is 5mL/h, and reception device is cylinder, and reception device is 20cm at syringe needle, spinning environment
Temperature is 25 DEG C.
(4) static spinning membrane prepared by vacuum drying step (3), trifluoroacetic acid solvent and moisture is removed, obtains the tool
There is hemostatic function biological medicinal membrane.
Scanning electron microscopic observation
The biological medicinal membrane with hemostatic function prepared to embodiment 1~5 is scanned electron microscopic observation.Fig. 1 is implementation
Polyglutamic acid/PLGA electrospun fibers scanning electron microscope diagrams of biological medicinal membrane with hemostatic function prepared by example 1.
As shown in Figure 1, the polyglutamic acid of the biological medicinal membrane/PLGA electrospun fibers have obvious core shell structure, and kernel is
PLGA, there is provided suitable mechanical strength, shell parcel polyglutamic acid, there is good hemostatic function and adhesion property；Nucleocapsid knot
Structure is compound on microcosmic level, and two kinds of composition combinations are more firm, difficult for drop-off, so that the life with hemostatic function
The hemostatic function of thing medical films is more long-acting；Compared with blend spinning, two kinds of material structures of the invention are clearly demarcated, and programmable is realized
Various physiological functions.Embodiment 2~5 prepare the biological medicinal membrane with hemostatic function with embodiment 1 prepare with
The biological medicinal membrane of hemostatic function has similar effect.
Anthemorrhagic performance
The biological medicinal membrane made from embodiment 2 is carried out as a control group as experimental group with Yunnan Baiyao and blank group
Zoopery.From new zealand white rabbit 15, liver middle period excision Hemorrhage Model is prepared, and embodiment 2 is used in bleeding part
Obtained biological medicinal membrane or Yunnan Baiyao simultaneously start timing, and with gauze pressing surface of a wound 30s, no blood, which oozes out, to stop blooding successfully.
Table 1 is each group sample bleeding stopping period result.98 ± the 4s of bleeding stopping period for antiadhesion barrier group of stopping blooding, the bleeding stopping period of Yunnan Baiyao group are
41 ± 13s, the bleeding stopping period of blank group are more than 300s, the results showed that hemostasis biological medicinal membrane haemostatic effect prepared by embodiment 2
Though not reaching the haemostatic effect of Yunnan Baiyao, its bleeding stopping period greatly shortens compared with blank control group, it may have good
Haemostatic effect.
The sample bleeding stopping period of table 1
| Group | Bleeding stopping period (s) |
| Yunnan Baiyao | 41±13 |
| Sample | 98±4 |
| Blank group | ＞ 300 |
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than the present invention is protected
The limitation of scope is protected, although being explained in detail with reference to preferred embodiment to the present invention, one of ordinary skill in the art should
Understand, technical scheme can be modified or equivalent substitution, without departing from the essence of technical solution of the present invention
And scope.
Claims (10)
1. a kind of biological medicinal membrane with hemostatic function, it is characterised in that be made up of fiber parallel connection, the fiber has kernel
And shell mechanism, the kernel are biodegradable polyesters, the shell is polyglutamic acid.
2. the biological medicinal membrane according to claim 1 with hemostatic function, it is characterised in that the biodegradable poly
Ester is Poly(D,L-lactide-co-glycolide, PLA or polycaprolactone.
3. the biological medicinal membrane according to claim 1 with hemostatic function, it is characterised in that the polyglutamic acid and life
The weight ratio of Biodegradable polyester is 1:5~1:1.
4. the biological medicinal membrane according to claim 1 with hemostatic function, it is characterised in that the polyglutamic acid weight is equal
Molecular weight is 900,000~1,500,000.
5. the biological medicinal membrane according to claim 1 with hemostatic function, it is characterised in that the biodegradable poly
Ester weight average molecular weight is 50,000~400,000.
6. the preparation method of the biological medicinal membrane with hemostatic function, its feature exist according to any one of Claims 1 to 5
In comprising the following steps：
(1) it is polyglutamic acid is soluble in water, polyglutamic acid solution is prepared, as shell spinning solution；
(2) biodegradable polyesters are dissolved in organic solvent, prepare biodegradable polyesters solution, it is molten as kernel spinning
Liquid；
(3) coaxial electrostatic spinning technology is used, shell spinning solution and kernel spinning solution are subjected to spinning, obtain electrostatic spinning
Film；
(4) static spinning membrane prepared by vacuum drying step (3), organic solvent and moisture are removed, obtained described with hemostasis work(
The biological medicinal membrane of energy.
7. the preparation method of the biological medicinal membrane according to claim 6 with hemostatic function, it is characterised in that described poly-
The concentration of polyglutamic acid is 1w/v%~10w/v% in glutamic acid solution.
8. the preparation method of the biological medicinal membrane according to claim 6 with hemostatic function, it is characterised in that the life
The concentration of biodegradable polyesters is 8w/v%~20w/v% in Biodegradable polyester liquid.
9. the preparation method of the biological medicinal membrane according to claim 6 with hemostatic function, it is characterised in that described to have
Solvent is dichloromethane, dimethyl sulfoxide (DMSO), trifluoroethanol, chloroform or trifluoroacetic acid.
10. the preparation method of the biological medicinal membrane according to claim 6 with hemostatic function, it is characterised in that described
In step (3), the condition of coaxial electrostatic spinning is：6~40kV of spinning voltage；Kernel spinning flow velocity is 0.1~10mL/h, shell
Spinning flow velocity is 0.1~5mL/h；Reception device is flat board or cylinder, and reception device is 20cm at syringe needle；Spinning environment temperature
Spend for 25 DEG C.
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Application publication date: 20180119 |