CN102908677A - Preparation method of anti-adhesion absorbable hernia patch - Google Patents
Preparation method of anti-adhesion absorbable hernia patch Download PDFInfo
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- CN102908677A CN102908677A CN2012104449379A CN201210444937A CN102908677A CN 102908677 A CN102908677 A CN 102908677A CN 2012104449379 A CN2012104449379 A CN 2012104449379A CN 201210444937 A CN201210444937 A CN 201210444937A CN 102908677 A CN102908677 A CN 102908677A
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Abstract
The invention relates to a preparation method of an anti-adhesion absorbable hernia patch. The preparation method adopts a two-step spinning method and includes first degrading a polycaprolactone (PCL) fiber layer with long period as a support base layer in electrospinning mode, then degrading a poly lactic-co-glycolic acid (PLGA) fibrous membrane as a function layer in electrospinning mode and reasonably selecting a solvent in the PLGA electrospinning process to obtain a double-layer fibrous membrane material with a double-layer fibrous membrane firmly. The fibrous membrane material prepared by the method combines excellent dynamic performance of PCL and histocompatibility of PLGA and can be widely used in the hernia repair technology.
Description
Technical field:
The present invention relates to degradable high polymer material and field of compound material, be specifically related to the preparation method that a kind of anti can absorb hernia paster.
Background technology:
At present, all can implant the hernia paster material in substantially all herniorrhaphys treats.Along with progress and the development of material, increasing material is designed to develop and is applied in herniorrhaphy.From nondegradable e-PTFE and polypropylene, to the degradable polypropylene-polyester composite of part, and the polyester of Wholly-degradable, also have extract in the animal body substantially without biomembrane of immunological rejection etc.Although the kind of hernia paster is so many, clinical research statistics finds, present hernia paster performance still exists a lot of problems, the pain that such as the generation of postoperative infection and superinfection, tissue adhesion, foreign body sensation etc. caused.Therefore, selecting suitable material and technology to prepare the more perfect hernia paster of performance is still a problem that needs to be resolved hurrily at present.
Electrostatic spinning technique is a kind of technology that can be from the nanometer to the micron even on large scale more, material structure be regulated and controled.This technology can be applicable to prepare the functional material that satisfies various application demands.For example can prepare and have anisotropic fibre structure, be applied to the muscle position and play the single-orientated effect of inducing cell; Fiber holes footpath and distribution can be regulated and controled, the filter membrane material of scale selection permeability can be obtained to have; Prepare three-dimensional rack mechanism, be used for induced tissue regeneration and arrange generating new tissue and structure.Breakthrough about electrostatic spinning technique has had a lot of reports in decades recently, yet, adopt this technology to be applied to the example of actual production also rare.
Summary of the invention:
The object of the present invention is to provide a kind of anti can absorb the preparation method of hernia paster.
To achieve these goals, the present invention proposes following technical scheme realization:
Anti can absorb hernia paster, it is characterized in that: hernia paster by support basic unit, functional layer forms; Described support basic unit is take first group of degradable high polymer material as material of main part; Described functional layer is added the macromolecule softener take second group of degradable high polymer material as material of main part; Support basic unit, functional layer all adopt electrostatic spinning technique to make.
Described anti can absorb hernia paster thickness 60 μ m～500 μ m.
Described first group of degradable high polymer material is PCL, number-average molecular weight 10,000～400,000.
In described functional layer, second group of degradable high polymer material accounts for 80%～100% of oeverall quality, and the macromolecule softener accounts for 1%～20% of oeverall quality.
Also comprise small-molecule drug in described functional layer.
Described small-molecule drug accounts for 0.05%～10% of second group of degradable high polymer material quality.
Described second group of degradable high polymer material is PLGA, number-average molecular weight 30,000～500,000, segment mol ratio L: G=90: 10～30: 70.
Described macromolecule softener is one or more in PCL, Merlon, PLA-b-PEG, number-average molecular weight 5,000～100,000.
Described small-molecule drug is one or more in Aminomethylbenzoic Acid, tranamic acid, 6-aminocaprolc acid, reptilase, thrombin, metronidazole, tinidazole, ornidazole.
Anti can absorb the preparation method of hernia paster, comprises the steps:
(1) preparation macromolecular solution: first group of degradable high polymer material is dissolved in corresponding cosolvent, is mixed with the solution that concentration is 10～60wt%; Second group of degradable high polymer material and macromolecule softener and small-molecule drug are dissolved in corresponding cosolvent, be mixed with the solution of concentration 5～50wt%, wherein second group of degradable high polymer material accounts for 80%～100% of gross mass, the macromolecule softener accounts for 1%～20% of gross mass, and small-molecule drug accounts for 0.05%～10% of biodegradable polymer quality;
(2) spin and support basic unit: controlling the spinning ambient temperature is 20-30 ℃, first group of degradable macromolecule solution that (1) is obtained is placed in the feed injector of electrospinning device, the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr opens high voltage power supply and feed injector pump, regulation voltage to 10～35KV, and the delivery rate of solution is 10～30 μ l/min, basic unit is supported on rotating drum;
(3) spin functional layer: controlling the spinning ambient temperature is 20-30 ℃, then the second group of biodegradable polymer, macromolecule softener, the small-molecule drug mixed solution that (1) are obtained are placed in the feed injector of electrospinning device, carry out spinning in the support basic unit that obtains in (2), the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr opens high voltage power supply and feed injector pump, regulation voltage to 10～35KV, and the delivery rate of solution is 10～30 μ l/min, obtains the electrospun fibers composite membrane on swing roller.
Described cosolvent is one or more in DMF, acetone, trifluoroethanol, hexafluoroisopropanol, THF, dimethyl acetylamide, dichloromethane.
Described electrospinning device is many spinning heads electrostatic spinning machine.
Beneficial effect of the present invention: adopt two step spin processes, at first the long PCL fibrous layer of electrospinning degradation cycle is as supporting basic unit, then spin the shorter PLGA fibrous membrane of degradation cycle as functional layer, by the choose reasonable of PLGA electrospinning Solvent, obtain firmly double-deck fiber film material of double-deck fibrous membrane combination; The fiber film material that adopts this invention to prepare combines the mechanical property of PCL excellence and the histocompatibility of PLGA, is widely used in the hernia repair art.
The specific embodiment:
Below describe the preferred embodiment of the present invention, but be not to limit the present invention.
Embodiment 1:
Be prepared as follows anti and can absorb hernia paster:
(1) preparation of solution: PCL (molecular weight 80000) is dissolved in trifluoroethanol, and being mixed with PCL concentration is the electrospinning solution of 10wt%; PLGA (molecular weight 60000), PCL (molecular weight 60000) and metronidazole are dissolved in DMF, and being mixed with concentration is the electrospinning solution of 40wt%, wherein PLGA: PCL=85: 15, PLGA: metronidazole=100: 5;
(2) spin and support basic unit: the PCL solution that (1) is obtained is placed in the feed injector of many spinning heads electrostatic spinning machine, controlling the spinning ambient temperature is 25 ℃, the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr; Open high voltage power supply and feed injector pump, regulation voltage to 10～35KV, the delivery rate of solution is 10～30 μ l/min, basic unit is supported on rotating drum;
(3) spin functional layer: PLGA, PCL, metronidazole mixed solution that (1) is obtained are placed in the feed injector of many spinning heads electrostatic spinning machine, controlling the spinning ambient temperature is 25 ℃, carry out spinning in the support basic unit that obtains in (2), the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr; Open high voltage power supply and feed injector pump, regulation voltage to 10～35KV, the delivery rate of solution is 10～30 μ l/min, obtains the electrospun fibers composite membrane on swing roller.
Embodiment 2:
Be prepared as follows anti and can absorb hernia paster:
(1) preparation of solution: PCL (molecular weight 150000) is dissolved in the mixed solvent of DMF and acetone (volume ratio is 8: 2), being mixed with PCL concentration is the electrospinning solution of 15wt%; PLGA (molecular weight 80000), PLA-b-PEG (molecular weight 80000), metronidazole, 6-aminocaprolc acid are dissolved in DMF, being mixed with concentration is the electrospinning solution of 35wt%, PLGA: PLA-b-PEG=90: 10, PLGA wherein: metronidazole: 6-aminocaprolc acid=100: 2: 2;
(2) spin and support basic unit: the PCL solution that (1) is obtained is placed in the feed injector of many spinning heads electrostatic spinning machine, controlling the spinning ambient temperature is 25 ℃, the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr; Open high voltage power supply and feed injector pump, regulation voltage to 10～35KV, the delivery rate of solution is 10～30 μ l/min, basic unit is supported on rotating drum;
(3) spin functional layer: PLGA, PLA-b-PEG, metronidazole, 6-aminocaprolc acid mixed solution that (1) is obtained are placed in the feed injector of many spinning heads electrostatic spinning machine, controlling the spinning ambient temperature is 25 ℃, carry out spinning in the support basic unit that obtains in (2), the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr; Open high voltage power supply and feed injector pump, regulation voltage to 10～35KV, the delivery rate of solution is 10～30 μ l/min, obtains the electrospun fibers composite membrane on swing roller.
In the double-deck hernia paster fibrous material for preparing: the fibre diameter 300nm of PCL～1.5 μ m, PLGA layer fibre diameter 1～3 μ m; The PLGA layer in vivo 6 months can be degradable; The degradation behavior of PLGA can not affect the mechanical property of PCL layer; The mechanical property of PCL can be kept 18 months in vivo, degraded gradually afterwards, its degradation cycle 3～5 years.
Claims (7)
1. anti can absorb the preparation method of the preparation method of hernia paster, it is characterized in that:
(1) preparation macromolecular solution: first group of degradable high polymer material is dissolved in corresponding cosolvent, is mixed with the solution that concentration is 10～60wt%; Second group of degradable high polymer material and macromolecule softener and small-molecule drug are dissolved in corresponding cosolvent, be mixed with the solution of concentration 5～50wt%, wherein second group of degradable high polymer material accounts for 80%～100% of gross mass, the macromolecule softener accounts for 1%～20% of gross mass, and small-molecule drug accounts for 0.05%～10% of biodegradable polymer quality;
(2) spin and support basic unit: controlling the spinning ambient temperature is 20-30 ℃, first group of degradable macromolecule solution that (1) is obtained is placed in the feed injector of electrospinning device, the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr opens high voltage power supply and feed injector pump, regulation voltage to 10～35KV, and the delivery rate of solution is 10～30 μ l/min, basic unit is supported on rotating drum;
(3) spin functional layer: controlling the spinning ambient temperature is 20-30 ℃, then the second group of biodegradable polymer, macromolecule softener, the small-molecule drug mixed solution that (1) are obtained are placed in the feed injector of electrospinning device, carry out spinning in the support basic unit that obtains in (2), the distance of regulating between spinning head and roller is 7～15cm, and the air velocity in environment is controlled at 0.5～0.8m
3/ hr opens high voltage power supply and feed injector pump, regulation voltage to 10～35KV, and the delivery rate of solution is 10～30 μ l/min, obtains the electrospun fibers composite membrane on swing roller.
2. anti according to claim 1 can absorb the preparation method of hernia paster, it is characterized in that: described first group of degradable high polymer material is PCL, number-average molecular weight 10,000～400,000.
3. anti according to claim 1 can absorb the preparation method of hernia paster, it is characterized in that: described second group of degradable high polymer material is PLGA, number-average molecular weight 30,000～500,000, segment mol ratio L: G=90: 10～30: 70.
4. anti according to claim 1 can absorb the preparation method of hernia paster, it is characterized in that: described macromolecule softener is one or more in PCL, Merlon, PLA-b-PEG, number-average molecular weight 5,000～100,000.
5. anti according to claim 1 can absorb the preparation method of hernia paster, it is characterized in that: described small-molecule drug is one or more in Aminomethylbenzoic Acid, tranamic acid, 6-aminocaprolc acid, reptilase, thrombin, metronidazole, tinidazole, ornidazole.
6. anti according to claim 1 can absorb the preparation method of hernia paster, it is characterized in that: described cosolvent is one or more in DMF, acetone, trifluoroethanol, hexafluoroisopropanol, THF, dimethyl acetylamide, dichloromethane.
7. anti according to claim 1 can absorb the preparation method of hernia paster, it is characterized in that: described electrospinning device is many spinning heads electrostatic spinning machine.
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| CN103638555A (en) * | 2013-11-15 | 2014-03-19 | 无锡中科光远生物材料有限公司 | Preparation method of hollow fiber used for blood vessel tissue engineering |
| CN104096272A (en) * | 2013-04-03 | 2014-10-15 | 中国科学院化学研究所 | Postoperation anti-infectious composite electrostatic-spinning nanometer fiber-film sheet for repairing hernia and preparation method thereof |
| CN105708581A (en) * | 2016-01-21 | 2016-06-29 | 东华大学 | Electrostatic-spun coated composite pelvic mesh and manufacturing method thereof |
| CN107148307A (en) * | 2016-02-29 | 2017-09-08 | 川澄化学工业株式会社 | Adherence preventing material |
| WO2017216609A1 (en) | 2016-06-15 | 2017-12-21 | Tubitak | Multifunctional hernia patch |
| JP2018518333A (en) * | 2015-04-29 | 2018-07-12 | ナノファイバー ソリューションズ、インク． | Multicomponent electrospun fiber scaffold |
| WO2019056774A1 (en) * | 2017-09-21 | 2019-03-28 | 上海松力生物技术有限公司 | Cruciate ligament regenerative implant and preparation method therefor and application thereof |
| CN111012950A (en) * | 2019-12-23 | 2020-04-17 | 华中科技大学同济医学院附属协和医院 | Composite repair patch and preparation method thereof |
| CN111035809A (en) * | 2019-12-04 | 2020-04-21 | 中山大学 | Double-layer composite nanofiber membrane with three-dimensional deformation structure and preparation method and application thereof |
| US10898608B2 (en) | 2017-02-02 | 2021-01-26 | Nanofiber Solutions, Llc | Methods of improving bone-soft tissue healing using electrospun fibers |
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| CN112891638A (en) * | 2021-01-18 | 2021-06-04 | 河南农业大学 | Preparation method of hernia patch with antibacterial effect |
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| US11737990B2 (en) | 2012-01-12 | 2023-08-29 | Nfs Ip Holdings, Llc | Nanofiber scaffolds for biological structures |
| US10941375B2 (en) | 2012-08-21 | 2021-03-09 | Nanofiber Solutions, Llc | Fiber scaffolds for enhancing cell proliferation in cell culture |
| US11246959B2 (en) | 2013-03-15 | 2022-02-15 | Nanofiber Solutions, Llc | Biocompatible fiber textiles for implantation |
| CN104096272A (en) * | 2013-04-03 | 2014-10-15 | 中国科学院化学研究所 | Postoperation anti-infectious composite electrostatic-spinning nanometer fiber-film sheet for repairing hernia and preparation method thereof |
| CN103638555A (en) * | 2013-11-15 | 2014-03-19 | 无锡中科光远生物材料有限公司 | Preparation method of hollow fiber used for blood vessel tissue engineering |
| JP2018518333A (en) * | 2015-04-29 | 2018-07-12 | ナノファイバー ソリューションズ、インク． | Multicomponent electrospun fiber scaffold |
| JP7219428B2 (en) | 2015-04-29 | 2023-02-08 | エヌエフエス アイピー ホールディングス、エルエルシー | Multicomponent electrospun fiber scaffold |
| CN105708581A (en) * | 2016-01-21 | 2016-06-29 | 东华大学 | Electrostatic-spun coated composite pelvic mesh and manufacturing method thereof |
| CN105708581B (en) * | 2016-01-21 | 2019-01-11 | 东华大学 | A kind of Static Spinning overlay film type basin with compound bottom sticking patch and preparation method thereof |
| CN107148307A (en) * | 2016-02-29 | 2017-09-08 | 川澄化学工业株式会社 | Adherence preventing material |
| WO2017216609A1 (en) | 2016-06-15 | 2017-12-21 | Tubitak | Multifunctional hernia patch |
| US10898608B2 (en) | 2017-02-02 | 2021-01-26 | Nanofiber Solutions, Llc | Methods of improving bone-soft tissue healing using electrospun fibers |
| US11806440B2 (en) | 2017-02-02 | 2023-11-07 | Nfs Ip Holdings, Llc | Methods of improving bone-soft tissue healing using electrospun fibers |
| WO2019056774A1 (en) * | 2017-09-21 | 2019-03-28 | 上海松力生物技术有限公司 | Cruciate ligament regenerative implant and preparation method therefor and application thereof |
| US11576927B2 (en) | 2018-12-11 | 2023-02-14 | Nanofiber Solutions, Llc | Methods of treating chronic wounds using electrospun fibers |
| CN111035809B (en) * | 2019-12-04 | 2021-06-01 | 中山大学 | Double-layer composite nanofiber membrane with three-dimensional deformation structure and preparation method and application thereof |
| CN111035809A (en) * | 2019-12-04 | 2020-04-21 | 中山大学 | Double-layer composite nanofiber membrane with three-dimensional deformation structure and preparation method and application thereof |
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| CN112891638A (en) * | 2021-01-18 | 2021-06-04 | 河南农业大学 | Preparation method of hernia patch with antibacterial effect |
| CN113209384A (en) * | 2021-05-08 | 2021-08-06 | 宁波市第一医院 | Pelvic floor patch for gynecology and preparation method thereof |
| CN113209384B (en) * | 2021-05-08 | 2022-03-25 | 宁波市第一医院 | Pelvic floor patch for gynecology and preparation method thereof |
| CN114225121A (en) * | 2021-12-22 | 2022-03-25 | 无锡中科光远生物材料有限公司 | Endothelialization part absorbable anti-adhesion fibrous membrane and preparation method thereof |
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Application publication date: 20130206 |