CN102758260A - Degradable submicron fiber membrane for postoperative adhesion prevention and preparation thereof - Google Patents
Degradable submicron fiber membrane for postoperative adhesion prevention and preparation thereof Download PDFInfo
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- CN102758260A CN102758260A CN2011101043960A CN201110104396A CN102758260A CN 102758260 A CN102758260 A CN 102758260A CN 2011101043960 A CN2011101043960 A CN 2011101043960A CN 201110104396 A CN201110104396 A CN 201110104396A CN 102758260 A CN102758260 A CN 102758260A
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Abstract
The invention relates to a degradable non-woven submicron fiber membrane and a preparation method thereof, as well as a purpose thereof for postoperative adhesion prevention of tissues and organs. A textile is prepared by adopting an electrostatic spinning method. The fiber membrane prepared by the method has good flexibility, air permeability and an effective tissue cell isolation function. A submicron structure with high specific surface area is also conductive to fast and uniform degradation of fiber. The fiber membrane after sterilization treatment can be used as a postoperative anti-adhesion membrane.
Description
Technical field
The present invention's " a kind of degradable submicron fiber film and preparation that is used for post-operation adhesion preventing " belongs to three types of medicine equipments of implantation, uses as the post-operation adhesion preventing film.
Background technology
Post-operation adhesion is operation one of an open question still, and theoretically, nearly all operation all relates to the problem of adhesion between the tissue.It can cause severe complications; Can cause adhesive ileus as forming adhesion in the abdominal cavity; Complication such as pelvic pain and female acyesis can be because of local adhesion causes postoperative epilepsy behind the craniotomy, and the thyroid gland postoperative can cause Secondary cases recurrent nerve injury etc. because of adhesion.Though most of patient can alleviate the state of an illness through non-operative treatment, is prone to outbreak repeatedly, can not effect a radical cure, and has influenced quality of life.And for the adhesive ileus of necessary operative treatment or the patient that need perform the operation once more, adhesion will obviously increase postoperative complication.For a long time, the surgeon is preventing to have done unremitting effort on the road of postoperative intestinal adhesion, and has obtained certain effect.But it is far from being enough obviously, only relying on consummate surgical procedures skill.
The method that prevents post-operation adhesion at present is a lot; Its mechanism of action also has nothing in common with each other, as: 1. fatty isolation method: the lipomicron in the human body can be protected the coarse surface of a wound extensively attached on peritonaeum, serous coat and the nethike embrane; The lubricated goldbeater's skin of isolating prevents the generation of mutual adhesion; Lipomicron gradually by the hydrolysis of lipase institute, is absorbed by lymphatic vessel in peritonaeum then simultaneously, to the effect of human non-toxic evil.This is the method for using the earliest that prevents adhesion, but because complicated operation, contraindication are more, and effect is not satisfactory, oneself seldom uses so far; 2. enzyme decomposition method: with the decomposes collagen fiber, can reach the purpose that prevents adhesion, but the side effect of enzyme is big with protease perfusion abdominal cavity, certain danger is arranged, effect is also uncertain, is difficult to clinically popularize; 3. physical method: adopt methods such as audio frequency, magnetic therapy, laser to improve local blood circulation, quicken the absorption of pathological product, thereby reach antiinflammation.Secondly for the spread effect of biosystem, local blood circulation can be improved, the quantity of macrophage can be increased.But instrument and equipment is expensive, and influences other normal cells and tissue easily.4. Biodegradable films: along with the deep understanding that adhesion is formed mechanism; The measure that Film with Preventing Adhesion forms also progressively updates; With the medical film of biodegradable is that the biological barrier material of representative is exactly wherein a kind of safe and efficient precautionary measures, is called " short-term barrier " method in the world.Its mechanism of action be with inflammation arranged or injured tissues and surrounding tissue keep apart; Fibroblast is to the invasion of the surface of a wound in the prevention surrounding tissue; And the controllability of its degradation time guarantees effectively to isolate to repair completion up to the mesothelial cell, thereby reaches the purpose that Film with Preventing Adhesion forms.The catabolite of biological absorbable medical film can be absorbed by the body or excrete through breathing and body fluid, so can not produce harm to human body.
In the whole bag of tricks of anti, adopting adherence preventing material is the main at present method that adopts as spacer after surgery.Desirable adherence preventing material should have excellent biological compatibility, suitable tissue adherence (need not sew up), fully wound coverage surface and have RT in enough bodies; Can degraded and absorbed and do not need second operation that it is taken out; Can effectively prevent the normal healing that adhesion forms does not influence wound again; Also should have certain mechanical strength and be convenient to implementation and operation etc.
PLGA is called polylactic acid-glycolic guanidine-acetic acid copolymer again, is one of the most promising biodegradated polymer materal at present.Its initial feed mainly is a starch, for example the starch in corn, the wheat.PLGA is the carbon dioxide and the water of biodegradation generation under field conditions (factors), can not produce any problem of environmental pollution.Behind implant into body.The phase I of its degraded is a hydrolytic process, generates water-soluble oligomer and lactic acid.Second stage resolves into carbon dioxide and water and other micromolecule under action of microorganisms.
PLGA is one of present comparatively ideal bio-medical material, has obtained drugs approved by FDA and has been used for biomedical every field, like carrier material, bone support, adherence preventing material and the organizational project etc. of medicine, hormone, vaccine and Gene Handling delivery systme.This material has good filming performance.Be used to prevent that the adhesion aspect from mainly being that the covering of PLGA film is placed in defect in the operation back, utilize the barrier action of film that wound tissue is effectively separated, treat that film absorbs fully, wound heals, and forms natural cover.Rely on the integrality of film, the PLGA film could effectively separate wound tissue, plays the effect of Film with Preventing Adhesion.After the cracking of PLGA film, fibr tissue and capillary are grown into immediately, should before wound healing, be kept perfectly so be placed on the PLGA film of site of injury.Behind the biological absorbable medical film implant into body, will degraded gradually in the time of design in advance, absorb, get into body metabolism with micromolecular form, finally form carbon dioxide and water, to breathe and the form of body fluid excretes, have security reliability.
Existing degradable Antiadhesive film forms by the polymer solution cast on the market.The product that changes technology production has following shortcoming: 1, product is waterproof airtight; 2, toxic solvent is residual; The degradation process of 3, self-catalysis formula causes local low pH value, thereby causes inflammatory reaction.
The electricity spinning at home and abroad has been ripe sub-micron fibers technology of preparing, but should technology as yet not clinical practice in this field of post-operation adhesion preventing film.Degradable Antiadhesive film with this technology preparation will have excellent specific properties such as permeable, ventilative, even degraded, low polymer dosage on the basis of effective separating tissues cell.Yet existing electric spining technology has following shortcoming: reported to meet the safety standard dicyandiamide solution stable inadequately, the easy blocking syringe needle is unfavorable for that industrialization produces for a long time.
Summary of the invention
The present invention relates to be used for the solvent system of electrostatic spinning technique, it comprises chloroform and methyl alcohol.In preferred embodiments, the proportioning of chloroform and methyl alcohol is (w/w) between 4: 1 to 1: 4 in the solvent system of the present invention.In preferred embodiments, also comprise carrene and dimethyl sulfoxide (DMSO) in the solvent system of the present invention.In preferred embodiments, the proportioning of chloroform, carrene, dimethyl sulfoxide (DMSO) and methyl alcohol is 1: 1: 1 in the solvent system of the present invention: 1 to 10: 10: 1: between 5 (v/v).
The invention still further relates to the method for carrying out electrostatic spinning, it is characterized in that utilizing solvent system of the present invention.In preferred embodiments, method of the present invention is carried out electrostatic spinning with the biodegradable polyester material as spinning material.In preferred embodiments; Biodegradable polyester material described in the method for the present invention can be DL lactic acid (PDLLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA); Polycaprolactone (PCL), chitin (chitosan) and their mixture or copolymer.In preferred embodiments, the molecular weight ranges of biodegradable polyester material described in the method for the present invention between 10kD between the 5000kD.In preferred embodiments, biodegradable polyester material described in the method for the present invention is 10～50% (w/w) in the concentration of said solvent system.
The invention still further relates to the submicron fiber film that adopts the inventive method preparation.In preferred embodiments, said submicron fiber film can be used for post-operation adhesion preventing, and is biodegradable.
The experiment proof is than the product of existing listing, and this film has the following advantages:
1) porous breathable.Nonwoven sub-micron fibers structure forms the effective aperture less than 1 micron, and porosity can effectively prevent cell-penetrating greater than 80% ventilated membrane when it helps mass exchange.Mostly existing product is hermetically sealable film.
2) no cytotoxicity.Fibroblast is attachment material surface and growth effectively, and the cytoactive on this film is close with the cytoactive on the Tissue Culture Plate.
3) evenly degraded.Based on its unique high-specific surface area structure, the sudden change degraded of self-catalysis formula has been avoided in the effectively diffusion fast of acid catabolite.Its tensile elasticity can be kept 2 months.Existing product can produce the sudden change degraded, is prone to cause inflammatory reaction.
The present invention has the following advantages for the improvement of traditional electrical spining technology in addition: organic solvent system used in the present invention has combined solubility; Rate of volatilization; The many-side of electrical conductivity and security is considered, can realize long-time high-speed production, stops up syringe needle in the conventional method of solution; Solvent evaporates is incomplete, difficult problems such as solution droplets splash
Description of drawings
Accompanying drawing 1 is depicted as electrospinning device, and wherein the label implication is following:
1 polymer solution;
2 syringe needles;
3 aloft polymer fibers;
4 ground connection collecting boaries;
5 high voltage direct current generating means;
6 electric spinning solution memories.
Specific embodiments
Embodiment
Embodiment 1
Solvent be chloroform and carbinol mixture (8: 2v/v), PLLA raw material (Purac, mean molecule quantity are 200000).Polymer concentration is 40mg/ml.
The electricity spinning solution is stored in the needle tubing, through the needle tubing pump spinning solution is extruded from No. 27 syringe needles.Discharge rate 5ml/hr.Through the HVDC electric generator voltage of 7kV in addition, syringe needle is 12cm (seeing accompanying drawing one) to the distance of collecting board.Spinning process is 1 hour, can be made into a slice 15 * 15cm size, and average thickness is 50 microns a tunica fibrosa, vacuumizes the removal residual solvent, packing and sterilization.
Comparative example 1
Carry out electrostatic spinning with following different prescription and spinning conditions.
The prescription and the spinning condition of electricity spinning solution
1 spinning process is observed:
A, b and c are the used spinning condition of bibliographical information, all occur the syringe needle stopping state in the spinning process in various degree, and promptly polymer solution volatilizees at the syringe needle place and solidifies, and the solution of obstruction flows out.The situation of obstruction syringe needle then appears in the solvent d that uses the present invention to improve, and spinning can be to carry out 2 hours under the situation of intervening until the experiment end at nobody.
2 configurations of surface are investigated (SEM) and porosity measurement
Electrospun fiber membrane surface metal spraying (JEOL JFC-1200 is gold-plated) back is with ESEM (FESEM; FEI Quanta 200, USA) observation configuration of surface and measure gained fibre diameter (n=100), the porosity of gained tunica fibrosa is measured with formula once:
2.1 configuration of surface
2.2PLGA fibre diameter (SEM mensuration)
| The preparation solvent, concentration (w/v) | Fibre diameter (nm) |
| A(40％) | 306±157 |
| B (25％) | 1016±293 |
| C(15％) | 652±227 |
| D(20％) | 523±155 |
Can find out that from accompanying drawing 2 electricity spins and can form non-woven fibrous structure, this structure has high porosity, the advantage of highly-breathable.See from technical parameter, the too little easy formation varicose fibers of solution concentration, the TENSILE STRENGTH of this fiber very a little less than, and the diameter of the big more fiber of solution concentration is also big more.Solvent B, C and D all can prepare the tunica fibrosa of homogeneous, and the advantage of solvent D is that its solvent properties can not cause syringe needle to stop up, and assurance preparation process is carried out smoothly.Mechanical test has subsequently also proved the superiority of D.
Accompanying drawing 2 is depicted as PLGA fiber SEM figure.
Wherein Fig. 2-1 is a solution of 40%PLGA; Fig. 2-2 is the b solution of 25%PLGA; Fig. 2-3 is the c solution of 15%PLGA; Fig. 2-4 is the d solution of 20%PLGA
2.3 optimize the prescription porosity
| The preparation solvent, concentration (w/v) | Material density (g/cm 3) | Characterize density (g/cm 3) | Porosity (%) |
| D(20％) | ?1.22 | ?0.249±0.013 | 79.6±1.1 |
[0045] The mechanical property of 3 electrospun fiber membranes
Instron 5848 microtester are used for extension test, and rate of extension is the 5mm/ branch, and sample length is 10mm for the 20mm width, and sample thickness is measured with micrometer caliper.
The result sees from extension test, and d spins the fiber that comes as the solvent electricity and has better tensile strength and bigger limiting strain.Do not receive any theoretical limit, this maybe to have higher polarity relevant with volatility with d, and the volatile solvent of high polarity helps electricity and spins.
Abovely describe the present invention with reference to embodiment preferred, but technical scheme of the present invention is not limited only to above-mentioned embodiment preferred, scope of the present invention only limits through appended claims.
Claims (10)
1. the solvent system that is used for electrostatic spinning technique, it comprises chloroform and methyl alcohol.
2. solvent system as claimed in claim 1, the proportioning of wherein said chloroform and methyl alcohol are (v/v) between 4: 1 to 1: 4.
3. solvent system as claimed in claim 1, it also comprises carrene and dimethyl sulfoxide (DMSO).
4. solvent system as claimed in claim 3, wherein the proportioning of chloroform, carrene, dimethyl sulfoxide (DMSO) and methyl alcohol is 1: 1: 1: 1 to 10: 10: 1: between 5 (v/v).
5. carry out the method for electrostatic spinning, it is characterized in that utilizing like the described solvent system of one of claim 1-4.
6. method as claimed in claim 5 is wherein carried out electrostatic spinning with the biodegradable polyester material as spinning material.
7. method as claimed in claim 6, wherein said biodegradable polyester material can be DL lactic acid (PDLLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), polycaprolactone (PCL), chitin (chitosan) and their mixture or copolymer.
8. method as claimed in claim 7, the molecular weight ranges of wherein said biodegradable polyester material between 10kD between the 5000kD.
9. method as claimed in claim 7, wherein said biodegradable polyester material is 10～50% (w/v) in the concentration of said solvent system.
10. adopt the submicron fiber film of making like the described method of one of claim 5-9.
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| CN2011101043960A CN102758260A (en) | 2011-04-25 | 2011-04-25 | Degradable submicron fiber membrane for postoperative adhesion prevention and preparation thereof |
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| CN2011101043960A CN102758260A (en) | 2011-04-25 | 2011-04-25 | Degradable submicron fiber membrane for postoperative adhesion prevention and preparation thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115023246A (en) * | 2020-01-14 | 2022-09-06 | 日本脏器制药株式会社 | Medical sheet |
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| US20020173213A1 (en) * | 2001-05-16 | 2002-11-21 | Benjamin Chu | Biodegradable and/or bioabsorbable fibrous articles and methods for using the articles for medical applications |
| CN1687494A (en) * | 2005-04-05 | 2005-10-26 | 中国科学院长春应用化学研究所 | Method of preparing superfie fiber formulation for carmustine |
| CN1876926A (en) * | 2006-07-04 | 2006-12-13 | 薛占强 | Biodegradable nanofiber nonwoven fabric capable of preventing postoperative adhesion and preparation thereof |
| CN101623517A (en) * | 2009-08-11 | 2010-01-13 | 广州迈普再生医学科技有限公司 | Medical anti-sticking membrane and preparation method thereof |
| CN101721739A (en) * | 2008-10-10 | 2010-06-09 | 陈东 | Polymer composite fiber surgical suture line capable of sustaining and controlling release of therapeutic medicaments and preparation method thereof |
| CN101829361A (en) * | 2009-03-10 | 2010-09-15 | 广州迈普再生医学科技有限公司 | Nano-bionic material for tissue repair and preparation method thereof |
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- 2011-04-25 CN CN2011101043960A patent/CN102758260A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020173213A1 (en) * | 2001-05-16 | 2002-11-21 | Benjamin Chu | Biodegradable and/or bioabsorbable fibrous articles and methods for using the articles for medical applications |
| CN1687494A (en) * | 2005-04-05 | 2005-10-26 | 中国科学院长春应用化学研究所 | Method of preparing superfie fiber formulation for carmustine |
| CN1876926A (en) * | 2006-07-04 | 2006-12-13 | 薛占强 | Biodegradable nanofiber nonwoven fabric capable of preventing postoperative adhesion and preparation thereof |
| CN101721739A (en) * | 2008-10-10 | 2010-06-09 | 陈东 | Polymer composite fiber surgical suture line capable of sustaining and controlling release of therapeutic medicaments and preparation method thereof |
| CN101829361A (en) * | 2009-03-10 | 2010-09-15 | 广州迈普再生医学科技有限公司 | Nano-bionic material for tissue repair and preparation method thereof |
| CN101623517A (en) * | 2009-08-11 | 2010-01-13 | 广州迈普再生医学科技有限公司 | Medical anti-sticking membrane and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115023246A (en) * | 2020-01-14 | 2022-09-06 | 日本脏器制药株式会社 | Medical sheet |
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Address after: 518028, room 1, building ten, Shenzhen biological incubation center, No. 302, Nanshan District hi tech, Shenzhen, Guangdong Applicant after: Shenzhen Feixiang Shiji Biological Co., Ltd. Address before: 518028 Guangdong city of Shenzhen province Futian District Shangbu road Shenzhen Kan building (room 1511) 15E Applicant before: Shenzhen Feixiang Shiji Biological Co., Ltd. |
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