CN100500228C - Biodegradable film having honeycomb structure - Google Patents
Biodegradable film having honeycomb structure Download PDFInfo
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- CN100500228C CN100500228C CNB2004800164491A CN200480016449A CN100500228C CN 100500228 C CN100500228 C CN 100500228C CN B2004800164491 A CNB2004800164491 A CN B2004800164491A CN 200480016449 A CN200480016449 A CN 200480016449A CN 100500228 C CN100500228 C CN 100500228C
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- China
- Prior art keywords
- thin film
- biodegradable
- ojosa
- phospholipid
- adherence preventing
- Prior art date
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- Expired - Lifetime
Links
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- 229920002988 biodegradable polymer Polymers 0.000 claims abstract description 15
- 239000004621 biodegradable polymer Substances 0.000 claims abstract description 15
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract description 11
- 239000004626 polylactic acid Substances 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 239000010409 thin film Substances 0.000 claims description 66
- 239000000463 material Substances 0.000 claims description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 229910001868 water Inorganic materials 0.000 claims description 19
- 229920000642 polymer Polymers 0.000 claims description 18
- 239000000758 substrate Substances 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 14
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- 229940117828 polylactic acid-polyglycolic acid copolymer Drugs 0.000 claims description 8
- -1 polytetramethylene carbonate Polymers 0.000 claims description 7
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- 238000005266 casting Methods 0.000 claims description 4
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- 238000001704 evaporation Methods 0.000 claims description 3
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
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Images
Abstract
The invention relates to a honeycomb film made of a biodegradable polymer which has biodegradation properties as an anti-adhesion membrane for preventing adhesion after an operation, is excellent in handling properties, and exhibits a satisfactory adhesion preventive effect stably over a desired period of time, and to a production process of the same. Above all, the invention provides an anti-adhesion membrane of a honeycomb film made of polylactic acid as a biodegradable polymer and a phospholipid and a production process of the same.
Description
Technical field
The present invention relates to be used to prevent the adherence preventing material of tissue adhesion.In more detail, relate to by the formed adherence preventing material of the Biodegradable film with ojosa.Adherence preventing material of the present invention is handled the property excellence, stablizes in during desirable, brings into play good preventing adhesiving effect.
Background technology
The tissue adhesion of one of physiological action that produces behind the surgical operation is defined as, and collagen fiber that the fibroblast that produces by being accompanied by tissue injury caused produce unusual combination of the surrounding tissue that causes and internal organs etc.This adhesion takes place with the probability of postoperative 90%, and when causing pain, organism malfunction etc., the patient can become problem with spirit, sensual misery.
Carried out a lot of research in order to address this problem all the time.For example be reduced to minimum, used water solublity adherence preventing materials such as sodium alginate aqueous solution, aqueous solution of sodium hyaluronate for adhesion is formed.But, though these have certain effect,, therefore also can flow to position in addition, the necessary position of anti owing to be water miscible, not only can not stay necessary position, and can cause the danger that normal position sticks together in addition.
Therefore, for tissue and other separate tissue that will damage, having studied will be as materials such as the silicon of physical barriers, vaseline, politef as adherence preventing material.Because the bioabsorbable material of these material right and wrong, though therefore abundant as the effect of barrier, being detained between long-term in vivo to have causes immunoreactive danger, cures the back and perform the operation once more etc. for their being taken out needs, becomes problem.
In order to address this problem, developed the adherence preventing material that uses as the natural polymer of bioabsorbable material.
Specifically, known have an adherence preventing material that uses oxidized cellulose, but when using the sponge of being made by oxidized cellulose, fabric, the cellulose cell easily by the space, move, therefore the problem that causes adhesion is arranged.For it is prevented, develop and used the adherence preventing material that constitutes by hyaluronate sodium and carboxymethyl cellulose.But,, produce the problem of difficult treatment because therefore these material water absorption height can adhere with the moisture of surgical instrument, affected part internal organs in addition.
Adherence preventing material, preferred cellulose cell can not flow to the shape of other tissues and are the materials biodegradable, that operability is high from a tissue.
The spy opens and discloses the porous adherence preventing material that the copolymer by lactic acid and caprolactone forms in the 2000-197693 communique.
The spy opens and has put down in writing in the 2001-157574 communique with biodegradable polymer and hydrophilic acrylamide polymer as main skeleton, have hydrophobic side chains when having added 1～50% and be dodecyl, hydrophilic side-chains and be thin film that the polymer of the amphipathic nature polyalcohol of lactose base or carboxyl constitutes with ojosa with and manufacture method.
Yet the polymer of employed base material is the high polymer of biocompatibility here, but infers that amphipathic nature polyalcohol decomposes, and generates acrylamides, and not talkative this analyte is certain safety to organism.If possible, hope is controlled at the use amount of this kind amphipathic nature polyalcohol minimum as far as possible.
Like this, use to be used in bio-tissue as purpose, when having the thin film of microstructure, biocompatibility becomes a very big problem.Therefore, hope is not only the polymer of use, be used to form microstructure reagent, be that the surfactant of amphipathic nature polyalcohol etc. also has biocompatibility and to the safety of organism.So, consider from guaranteeing the safety aspect, also wish to improve the amount of polymer, the use amount of control surface activating agent.
At present, have the biodegradability of appropriateness and biocompatibility, processing excellence, stable and adherence preventing material that bring into play preventing adhesiving effect does not well also exist during desirable, is expecting the appearance of this material.
Summary of the invention
The Biodegradable film that present inventors find to have ojosa is the property handled excellence, stablize and bring into play well the adherence preventing material of preventing adhesiving effect in during desirable.
In addition, also find by with phospholipid as the surfactant compatibility in biodegradable polymer, under high humility, cast then, base material as cell culture is also useful, can access the thin film with ojosa of biocompatibility excellence, and this thin film has the effect of the adhesion that prevents operative site etc., and then has finished the present invention.
That is, the present invention relates to by having adherence preventing material ojosa, that biodegradable thin film forms, the average space internal diameter that relates to by ojosa is the adherence preventing material that the biodegradable thin film below the 20 μ m forms.
And, the manufacture method that relates to adherence preventing material, promptly, manufacture method as this adherence preventing material, the organic solvent solution of biodegradable polymer is cast dewfall when this organic solvent is slowly evaporated, on the surface of this casting liquid, the small water droplet that evaporation forms by this dewfall on substrate under the atmosphere of relative humidity 50～95%, obtain having the Biodegradable polymeric thin film of ojosa thus, and with its use.
In the optimal way of the present invention, the biodegradable thin film that will have ojosa is as physical barriers, is configured in operative site and is adjacent between the tissue, and the connection of restriction tissue reduces the formation of tissue adhesion thus.
As being used to make the employed biodegradable polymer of Biodegradable film of the present invention, from the deliquescent viewpoint organic solvent, biodegradable aliphatic polyesters such as preferred polylactic acid, polylactic acid-polyglycolic acid copolymer, poly butyric, polycaprolactone, 10PE27, poly adipate succinic acid ester, fatty poly-ester carbonates such as polytetramethylene carbonate diol, poly-ethylene carbonate ester etc. wherein, from obtain easily, viewpoint such as price considers preferred polylactic acid, polylactic acid-polyglycolic acid copolymer, polycaprolactone.
For making ojosa easy, favorable reproducibility, preferably on the basis of above-mentioned biodegradable polymer, use amphipathic nature polyalcohol.As amphipathic nature polyalcohol, consider as adherence preventing material and use, preferably nontoxic, can use the polyethylene/polypropylene glycol block copolymer; Acrylamide polymer is main skeleton, have hydrophobic side chains simultaneously is that dodecyl, hydrophilic side-chains are the amphipathic nature polyalcohol of lactose base or carboxyl; The perhaps ion complex that forms with the anionic property macromolecule and the chain alkyl ammonium salt of the nucleic acid of heparin, dextran sulfate, DNA and RNA etc.; Water soluble proteins such as gelatin, collagen, albumin are the amphipathic nature polyalcohol of hydrophilic radical etc.
In addition, also can use biodegradable and have amphipathic polymer. such polymer for example can be lifted polylactic acid-polyglycol block copolymer, poly-epsilon-caprolactone-polyethyleneglycol block copolymer, polymalic acid-polymalic acid Arrcostab block copolymer etc.
For making ojosa easy, favorable reproducibility, can also on the basis of above-mentioned biodegradable polymer, phospholipid be added as surfactant.
Phospholipid is the material that constitutes the organism film, because originally just in vivo, so the biocompatibility height, in drug delivery, also being utilized, safety is also high.And in the present invention, the phosphorus matter fat that uses as surfactant can easily obtain.
No matter the phospholipid that uses among the present invention extracts from animal tissue, still is synthetic, and which kind of source all can be used.As phospholipid, wish to use the material that is selected from PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, Phosphatidylserine, phosphatidyl glycerol and their derivant.Be preferably PHOSPHATIDYL ETHANOLAMINE, L-α-DOPE more preferably.
When making honeycomb structure of the present invention, because it is necessary forming small water droplet particle on polymer solution, therefore must be non-water-soluble as the organic solvent that uses. can enumerate halogen such as chloroform, dichloromethane as an example is organic solvent, aromatic hydrocarbon such as benzene,toluene,xylene, esters such as ethyl acetate, butyl acetate, water-insoluble ketone such as methyl iso-butyl ketone (MIBK), Carbon bisulfide etc.These organic solvents can use separately, perhaps also the synthetic mixed solvent of these group of solvents can be used.
The concentration that is dissolved in the total polymer of biodegradable polymer in them and amphipathic nature polyalcohol is 0.01～10wt%, more preferably 0.05～5wt%.When polymer concentration was lower than 0.01wt%, the thin film mechanical strength that obtains is not enough, and was not preferred.When surpassing 10wt%, the excessive concentration of polymer can't obtain sufficient ojosa.In addition, the ratio of components of biodegradable polymer and amphipathic nature polyalcohol is 99: 1～50: 50 (wt/wt).The composition of amphipathic nature polyalcohol then can't obtain the ojosa of homogeneous below 1; This is formed 50 when above, and the stability of the honeycomb structure that then obtains, particularly mechanical stability are bad, so not preferred.
Equally, being dissolved in biodegradable polymer in the above-mentioned solvent and total solution concentration of phospholipid is 0.01～10wt%, is preferably 0.05～5wt%.When the concentration of polymer was lower than 0.01wt%, the mechanical strength of the thin film that obtains was not enough, and is not preferred.When surpassing 10wt%, solution concentration is too high, can't obtain sufficient ojosa.In addition, the ratio of components of biodegradable polymer and phospholipid is weight ratio 1: 1～1000: 1 (wt/wt). with respect to Biodegradable polymeric, phospholipid can't obtain the ojosa of homogeneous 1/1000 when following; This weight ratio is at 1: 1 when above, and as self supportive of film, cost is not high, uneconomical yet, and is therefore not preferred.
Among the present invention, this polymer organic solvent solution is cast on substrate, the modulation honeycomb structure, can use inorganic material such as glass, metal, silicon chip as this substrate, the macromolecule of organic solvent-resistant excellences such as polypropylene, polyethylene, polyether-ketone, liquid such as water, liquid paraffin, aqueous polyethers.Wherein, when base material makes water,, can easily this tectosome be taken out separately from substrate by bringing into play distinctive self supportive of this honeycomb structure, therefore preferred.
The principle that forms ojosa among the present invention is as follows.Seized latent heat when hydrophobic organic solvent volatilizees, the surface temperature of cast films descends, the drop of small water in polymer solution surface coagulation, adhere to.Because the effect of the hydrophilic parts in the polymer solution, the surface tension between water and the hydrophobic organic solvent reduces, and therefore, the water micropartical becomes one with coagulation, becomes stable.Be accompanied by the evaporation of solvent, become hexagonal drop with filling shape arrangement the most closely, last water vapors away, and polymer left behind to be arranged with regular cellular shape.Therefore, as the environment of this thin film of modulation, be 50～95% scopes preferably at relative humidity.Below 50%, then the dewfall on cast films is insufficient; More than 95%, be difficult to control environment, therefore not preferred.The size of the space internal diameter of the ojosa that obtains like this is 0.1～20 μ m.As long as in this scope, can be suitable as adherence preventing material and use.
The thin film of Zhi Zuoing like this, the surface has ojosa, under the fully thick situation of thickness, becomes that the hole does not connect, level and smooth face with the contacted back side of substrate.And when thickness is thinner than water droplet big or small, obtained the thin film that the hole connects.
Therefore, according to application target, select the thin film that connects or do not connect.
If from the viewpoint of anti, in order to prevent the cellulosic circulation between internal organs, the thin film that preferably uses the hole not connect.In addition, the face that preferably will have ojosa contacts with affected part, and its reason is, in the blood of affected part generation, the inside that tissue fluid can be absorbed into ojosa, can prevent oozing out to the outside.
Adherence preventing material of the present invention is considered from the viewpoint that improves mechanical strength, also can be for lamination the mode of ojosa body thin film more than 2 layers.The number of plies as laminated ojosa body thin film, viewpoint from the thin film flexibility, preferred 2～15 layers, more preferably 2～10 layers. thus, adherence preventing material then can comprehensively have the mechanical strength that polymer had that constitutes each thin film, tissue adhesion, characteristic such as bioabsorbable.
Lamination ojosa body thin film and the adherence preventing material that forms can be made by following mode, that is, with appropriate solvent with the moistening of laminated ojosa body thin film, lamination then, perhaps each ojosa body thin film of lamination, with after the appropriate solvent moistening, drying.Solvent as the moistening dry film does not come the solvent of moistening to get final product so long as do not dissolve the honeycomb structure thin film, can use any solvent.For example preferably make the aqueous solution of the inorganic salts of water, sodium chloride, calcium chloride etc. in addition, can add organic solvents such as ethanol, methanol, propanol.
The thickness of ojosa body thin film is not particularly limited, but considers from the viewpoint of flexibility, preferably below 500 μ m, more preferably below 200 μ m.In addition, consider from the viewpoint of the property handled, more than the preferred 1 μ m, more preferably more than the 3 μ m.
Adhesion when adherence preventing material of the present invention is particularly preferred for preventing surgical operation.For example be used to prevent abdominal to diseases such as liver, spleen, pancreas, kidney, uterus, ovaries, during the suture operation of achilles tendon, nerve etc. etc., the adhesion on the bio-tissue surface of injuring owing to operation.
The using method of adherence preventing material of the present invention sticks after affected part for the peristome with the ojosa body thin film, the moisture of absorbing blood, tissue fluid etc., being fixed on affected part. owing to moisture, therefore need not be sewn on the affected part in peristome absorbing blood, tissue fluid etc.
And, few when the moisture of affected part, fixing when insufficient, adherence preventing material of the present invention is sticked behind affected part, can also be from external complement moisture, promote the fixing of this material. as moisture from external complement, so long as the harmless aqueous solution of affected part is got final product, can use any solution, but preferred normal saline or Ringer's solution.
And, under the thin film dipped state in water of the present invention gelation, dissolving can not take place, therefore can not adhere on the surgical instrument, handle easily.
In addition, adherence preventing material of the present invention can carry out the sterilization treatment of for example ethanol sterilization, gamma-radiation sterilization, the sterilization of electronics line, ethylene oxide gas sterilization etc., can improve safety by these processing.
Description of drawings
Fig. 1 is the optical microscope photograph of adherence preventing material of the present invention.
Fig. 2 is the electron micrograph of the thin film with ojosa that obtains among the embodiment 4.
Fig. 3 is the electron micrograph of the thin film with ojosa that obtains among the embodiment 5.
Fig. 4 is the optical microscope photograph of the thin film with ojosa that obtains among the embodiment 6.
Fig. 5 is the optical microscope photograph of the thin film with ojosa that obtains among the embodiment 7.
Fig. 6 is the optical microscope photograph of the thin film with ojosa that obtains among the embodiment 8.
The specific embodiment
Below, by embodiment embodiments of the present invention are described, but the present invention is not subjected to its any qualification.
Embodiment
Embodiment 1
In the chloroformic solution (5g/L) of polylactic acid (molecular weight 100000) with 10: 1 mixed as the polyacrylamide copolymer (weight average molecular weight: 85 shown in the chemical compound formula 1 of amphipathic nature polyalcohol, 000), on glass substrate, cast, under the condition of room temperature, humidity 70%, leave standstill, slowly solvent flashing is modulated honeycomb structure thus.The size of the space internal diameter of the ojosa of the tectosome that obtains like this is 5 μ m, and thickness is 13 μ m.Optical microscope photograph as shown in Figure 1.
Embodiment 2
(copolymer was than 75: 25 at the polylactic acid-polyglycolic acid copolymer, molecular weight 100000) in the chloroformic solution (5g/L), with the polyacrylamide copolymer of 10: 1 mixed as amphipathic nature polyalcohol, on glass substrate, cast, under the condition of room temperature, humidity 70%, leave standstill, slowly solvent flashing is modulated honeycomb structure thus.The size of the space internal diameter of the ojosa of the tectosome that obtains like this is 5 μ m, and thickness is 13 μ m.
The structural formula of employed polyacrylamide copolymer is as follows.
(m, n represents recurring unit, m.n=1: 4.)
Comparative example 1
The chloroformic solution (100g/L) of polylactic acid (molecular weight 100000) is cast on glass substrate, at room temperature left standstill, remove by natural drying and desolvate, make cast films thus.
Comparative example 2
The chloroformic solution (100g/L) of polylactic acid-polyglycolic acid copolymer (copolymer than 75: 25, molecular weight 100000) is cast on glass substrate, at room temperature left standstill, remove by natural drying and desolvate, make cast films thus.
Embodiment 3
After male SPF does not have a mao rat (average weight 250g) and anaesthetizes by lumbar injection, hara kiri, expose stomach, at stomach bottom wall crust make wound about 8mm thereafter, stick the anti material (3cm is square) that embodiment 1,2 and comparative example 1,2 obtain respectively, every rat is pasted one piece. after having sticked adherence preventing material, cut open inspection after 1 week, perusal adhesion state, the adhesion state of each rat result shown in following table 1.
The honeycomb structure of embodiment 1,2 thin film dipped can gelation in water, can not dissolve, because thin film softness, also easy to sticking of affected part, processing is good. and do not have tangible inflammatory reaction, the biocompatibility of the adherence preventing material that obtains by the present invention is good as can be known.The cast films of comparative example 1,2 lacks flexibility, in case produce gauffer, non-resilient, to the difficulty that sticks of affected part, therefore not talkative operability is good.
The results are shown in table 1.
Table 1
Embodiment 4
In the chloroformic solution (5g/L) of polylactic acid (molecular weight 100000) with 10: 1 mixed DOPE as surfactant, on glass substrate, cast, under the condition of room temperature, humidity 70%, leave standstill, slowly solvent flashing is modulated the thin film with ojosa thus.In the tectosome that obtains like this, the size that constitutes each space, hole internal diameter of ojosa is 5 μ m, and thickness is 13 μ m, is the film that does not connect.If thin film is nebulousurine. polylactic acid film is made of general casting method, then be water white, but when having ojosa as the present invention, then owing to scattering of light, thin film is nebulousurine.The SEM photo is shown in Fig. 2.
Embodiment 5
In the chloroformic solution (5g/L) of polylactic acid (molecular weight 100000) with 200: 1 mixed DOPE as surfactant, on glass substrate, cast, under the condition of room temperature, humidity 70%, leave standstill, slowly solvent flashing is modulated the thin film with ojosa thus.In the tectosome that obtains like this, the size that constitutes each space, hole internal diameter of ojosa is 5 μ m, and thickness is 13 μ m, is the film that does not connect.Thin film is nebulousurine.Judge thus and generated ojosa similarly to Example 4.The SEM photo is shown in Fig. 3.
Embodiment 6
In the chloroformic solution (5g/L) of polylactic acid (molecular weight 100000) with 800: 1 mixed DOPE as surfactant, on glass substrate, cast, under the condition of room temperature, humidity 70%, leave standstill, slowly solvent flashing is modulated the thin film with ojosa thus.In the tectosome that obtains like this, the size that constitutes each space, hole internal diameter of ojosa is 5 μ m, and thickness is 13 μ m, is the film that does not connect.Thin film is nebulousurine.Judge thus and generated ojosa similarly to Example 4.Light micrograph is shown in Fig. 4.
Embodiment 7
In the chloroformic solution (5g/L) of polylactic acid-polyglycolic acid copolymer (molecular weight 101000) with 10: 1 mixed DOPE as surfactant, on glass substrate, cast, under the condition of room temperature, humidity 70%, leave standstill, slowly solvent flashing is modulated the thin film with ojosa thus.In the tectosome that obtains like this, the size that constitutes each space, hole internal diameter of ojosa is 3 μ m, thickness is 10 μ m, if be the film that does not connect. thin film is nebulousurine. and polylactic acid film is made of general casting method, then be water white, but when having ojosa as the present invention, then owing to scattering of light, thin film is nebulousurine. light micrograph is shown in Fig. 5.
Embodiment 8
In the chloroformic solution (5g/L) of polylactic acid-polyglycolic acid copolymer (molecular weight 101000) with 200: 1 mixed DOPE as surfactant, on glass substrate, cast, under the condition of room temperature, humidity 70%, leave standstill, slowly solvent flashing is modulated the thin film with ojosa thus.In the tectosome that obtains like this, the size that constitutes each space, hole internal diameter of ojosa is 5 μ m, and thickness is 10 μ m, is the film that does not connect. thin film is nebulousurine. and judges thus to have generated ojosa similarly to Example 7.Light micrograph is shown in Fig. 6.
Comparative example 3
The chloroformic solution (5g/L) of polylactic acid (molecular weight 100000) is studied the thin film with ojosa with the method identical with embodiment 4.But, do not form ojosa, made inhomogenous thin film.
Comparative example 4
The chloroformic solution (5g/L) of DOPE is studied honeycomb structure with the method identical with embodiment 1.But, do not make film, there is not self supportive yet.
In order to confirm the effect of anti-biological body adhesion of the present invention, use the intra-abdominal adhesions model of rat to experimentize.
The intra-abdominal adhesions model be with rat after intraperitoneal gives pentobarbital sodium (30mg/kg pentobarbital sodium inj, big Japanese pharmacy (strain)) anesthesia, back fixation, shave off the hair of abdominal part, carry out disinfection with ethanol for disinfection afterwards, reuse betadin disinfectant solution is sterilized operative region, cut 3～4cm along the abdominal part median line afterwards, expose caecum. at certain area (1～2cm of the caecum that exposes
2) on, the gauze friction of using the bacterium of going out is until petechial hemorrhage occurring.After caecum is put back into the abdominal cavity, stick adherence preventing material, the Musclar layer of cut-away portions is sewed up continuously skin closure 4～5 pins.After with the betadin disinfectant solution wound portion being carried out disinfection, put back in the cage.
Postoperative 7 days, with the rat laparotomy under the pentobarbital sodium anesthesia, the Intraabdominal adhesion degree of perusal is marked according to following standard.
Grade separation
Grade 0 (score 0): the state of adhesion not.
Grade 1 (score 1): but the adhesion of small delamination.
Grade 2 (score 2): among a small circle, can be anti-live the slight adhesion of slight traction.
Grade 3 (score 3): visible very firm adhesion or the state that sticks together more than at least 2 places.
Class 4 (score 4): stick together more than 3 places.
Embodiment and comparative example are as follows.
Embodiment 9
The thin film that uses embodiment 5 to obtain has been confirmed the preventing adhesiving effect of organism.
Comparative example 5
Identical with the operation of above-mentioned intra-abdominal adhesions model, do not use adherence preventing material to sew up.
Comparative example 6
Use Sepra thin film (hyaluronate sodium and carboxymethyl cellulose, the about 55 μ m of thickness, scientific research pharmacy (strain)) to implement the intra-abdominal adhesions model.
The intra-abdominal adhesions degree of each animal is marked according to grade separation, and (mean ± S.E.) represent is shown in table 2 to the result with meansigma methods ± standard deviation.
It is relative therewith that the average adhesion of comparative example 5 (no thin film) must be divided into 3.0 ± 0.3., and the average adhesion of embodiment 7 must be divided into 1.6 ± 0.5, and the adhesion score of comparing with comparative example 5 reduces.Compare with the adhesion score (1.8 ± 0.7) of comparative example 6 (Sepra thin film) equally, the adhesion score also reduces.
Adherence preventing material of the present invention is compared when not using adherence preventing material, has a significant effect.In addition, compare, also have preventing adhesiving effect with the Sepra thin film of the comparative example of using in the present reality 6, and since the such cohesiveness of example 6 thin film without comparison therefore handle easily.
Table 2
Intra-abdominal adhesions model evaluation result
Industrial applicability
Biodegradable film with ojosa of the present invention can be used as adherence preventing material Be applicable to organism.
Claims (12)
1. adherence preventing material, it is made of the biodegradable thin film with ojosa, this thin film is made of Biodegradable polymeric and surfactant, it is characterized in that, described surfactant is a phospholipid, and the weight ratio of described Biodegradable polymeric and phospholipid is 1:1～1000:1.
2. adherence preventing material as claimed in claim 1 is characterized in that, the aperture, average space of ojosa is below the 20 μ m.
3. adherence preventing material as claimed in claim 1 or 2 is characterized in that only the one side at thin film has ojosa.
4. have the biodegradable thin film of ojosa, it is made of biodegradable polymer and surfactant, it is characterized in that, this surfactant is a phospholipid, and the weight ratio of described biodegradable polymer and phospholipid is 1:1～1000:1.
5. the biodegradable thin film with ojosa as claimed in claim 4, wherein this biodegradable polymer is biodegradable aliphatic polyester.
6. the biodegradable thin film with ojosa as claimed in claim 5, wherein this biodegradable aliphatic polyester is at least one polymer that is selected from polylactic acid, polylactic acid-polyglycolic acid copolymer, poly butyric, polycaprolactone, 10PE27, poly adipate succinic acid ester, polytetramethylene carbonate diol, the poly-ethylene carbonate ester.
7. as any one described biodegradable thin film of claim 4～6, it is characterized in that this Biodegradable polymeric is polylactic acid or polylactic acid-polyglycolic acid copolymer with ojosa.
8. as claim 4 or 5 described biodegradable thin film with ojosa, wherein this phospholipid is selected from PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, Phosphatidylserine, phosphatidyl glycerol.
9. the described biodegradable thin film with ojosa of claim 8 is characterized in that wherein this phospholipid is L-α-PHOSPHATIDYL ETHANOLAMINE.
10. the biodegradable thin film with ojosa as claimed in claim 9 is characterized in that this phospholipid is L-α-DOPE.
11. an adherence preventing material is made of claim 4 or 5 described biodegradable thin film.
12. manufacture method as claim 1 or 11 described adherence preventing materials, it is characterized in that, the organic solvent solution of Biodegradable polymeric and phospholipid is cast on substrate under the atmosphere of relative humidity 50～95%, with the slow evaporable while of this organic solvent, make it at this casting liquid surface sweating, obtain having the Biodegradable polymeric thin film of ojosa by the small water droplet of dewfall generation by evaporation, and it is used, wherein saidly be dissolved in Biodegradable polymeric in the organic solvent and the total concentration of phospholipid is 0.01-10wt%.
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| CN102600738B (en) * | 2012-02-21 | 2014-10-15 | 东华大学 | Degradable hollow fiber membrane and preparation method thereof |
| CN102580578B (en) * | 2012-02-21 | 2015-05-13 | 东华大学 | Degradable hollow fiber membrane and application thereof |
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| CN107001615A (en) * | 2015-06-19 | 2017-08-01 | 东丽株式会社 | Polymeric membrane and the adherence preventing material obtained using it |
| CN107001615B (en) * | 2015-06-19 | 2020-05-08 | 东丽株式会社 | Polymer film and anti-blocking material obtained using same |
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