CN104096272A

CN104096272A - Postoperation anti-infectious composite electrostatic-spinning nanometer fiber-film sheet for repairing hernia and preparation method thereof

Info

Publication number: CN104096272A
Application number: CN201310116406.1A
Authority: CN
Inventors: 郑建芬; 王伟红; 韩志超
Original assignee: Institute of Chemistry CAS
Current assignee: Institute of Chemistry CAS
Priority date: 2013-04-03
Filing date: 2013-04-03
Publication date: 2014-10-15

Abstract

The invention relates to a postoperation anti-infectious composite electrostatic-spinning nanometer fiber-film sheet for repairing hernia and a preparation method thereof. The hernia-repairing sheet comprises a polymer nanometer fiber-membrane base sheet prepared through an electrostatic spinning method, and a biodegradable high-molecular nanometer fiber functional membrane which is connected with the polymer nanometer fiber-membrane base sheet, is loaded with an anti-infectious medicine and is obtained through an electrostatic spinning method. The polymer nanometer fiber-membrane base sheet is soft and good in mechanical properties, does not cause damage of internal organs and enables an internal organ to be fixedly disposed at a postoperation recovery position. The electrostatic-spinning nanometer fiber functional membrane loaded with the anti-infectious medicine has appropriate degradation speed, and the anti-infectious medicine is gradually released along with degradation of the material, so that postoperation infection and inflammation caused by wound pollution are effectively prevented. The hernia-repairing sheet is capable of effectively reducing inflammation reaction caused by postoperation infection and reducing patient pain after being implanted into a human body for repairing hernia.

Description

Anti-infective composite electrostatic spinning nano fibrous membrane hernia patch and preparation method thereof after being used for performing the operation

Technical field

The present invention relates to for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after clinical operation, be particularly related to and comprise that electrostatic spinning nano fibrous membrane substrate and the load being connected with described electrostatic spinning nano fibrous membrane substrate have the compound hernia patch of the electrostatic spinning nano fiber functional membrane of anti-infectives, and should be for the preparation method of anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after clinical operation.

Background technology

Hernia is also hernia or small intestine-QI.Briefly, hernia is tearing of abdominal wall muscle tissue or broken hole, and the organs such as patient's small intestinal or tissue leave by this broken hole other position that health is charged in origin-location.As treatment not in time, former abdominal-wall defect can be increasing, situation severe patient, also occurred originally can Hui Na lump can not push back in body, simultaneously with abdominal colic, vomiting, abdominal distention, outstanding enteric cavity or other intra-abdominal organs are blocked by hernia ring, can not return again and include abdominal cavity in, medically be referred to as hernia incarceration, this situation very easily causes internal organs ischemia, necrosis in enteric cavity or other abdomens, as the entail dangers to life of performing the operation not in time.Conservative estimation, the annual nearly 2,000,000 routine inguinal hernia patients of China, and the patient who really does groin repairing operation approximately only has 80,000 examples, that is to say that untreated more than 190 ten thousand patients are also standing various miseries.

According to official's data of American family doctors'associations, except part juvenile, hernia cannot spontaneous recovery.At present, herniorrhaphy is the only selection of curing abdominal hernia.Herniorrhaphy refers to by operation treating of hernia, can be divided into three major types: traditional hernioplasty, hernia sticking patch are without tension force kposthesis (or claiming fill-type kposthesis) and hernia peritoneoscope kposthesis.Current hernia sticking patch has become clinician without tension force kposthesis and has treated the routine operation that abdominal hernia is taked, and hernia patch is that hernia sticking patch is without the embedded material of tension force kposthesis and hernia peritoneoscope kposthesis.Hernia peritoneoscope kposthesis belongs to Wicresoft, but does not also extensively carry out now, technical not as hernia sticking patch is without tension force kposthesis maturation.

The development of artificial patching material can be traced back to the Inguinal Hernia Herniorrhaphy that Laroque in 1919 carries out with wire netting the earliest, but due to its not folding, and poor compliance fails commercialization to be just eliminated.Appearance and fast development in mid-term in 20th century along with novel artificial synthetic material, the technology of utilizing high-molecular organic material to carry out hernia repairing starts to be applied to clinical, and has obtained significant curative effect.Yet although the hernia patch of being prepared by various polymeric materials has brought a lot of advantages in clinical practice, due to the rejection in host, all there is certain infection problems in the hernia patch of being prepared by various polymeric materials.As most widely used nondegradable polypropylene type hernia patch at home and abroad at present, because of its quality harder, can cause comparatively serious intestinal adhesion and affect intestinal function, even cause intestinal obstruction and intestinal fistula, simultaneously, this hernia patch has the trend of contraction, and its shrinkage factor can reach more than 30%, these defective effects the evaluation of its final clinical performance.Polyesters hernia patch is compared with polypropylene hernia patch, and the pliability of polyesters hernia patch is good, but the ability of tension stress is only the former 1/3, causes the relapse rate of hernia high.Expanded PTFE hernia patch (ePTFE hernia patch), hernia patch for microporosity biomaterial, it is pliable and tough smooth, compliance is good, mechanical performance is superior compared with polypropylene net, generally can not cause the generation of intestinal fistula, but because it is poor with the adhesion of abdominal part surrounding tissue after implanting, while is due to the existence of micropore, make antibacterial be easy to hide, therefore the fastness after repairing and anti-infection ability are also not as good as polypropylene hernia patch and polyesters hernia patch, and ePTFE hernia patch is expensive, make it in clinical extensive use, also have at present certain difficulty.The implantation that can absorb hernia patch (as polyglycolic acid hernia patch (polyglycolic acid) and poly (glycolide-lactide) hernia patch (poly (lactic-co-glycolic acid))) due to reduced and internal organs between the harm of adhesion, and intestinal fistula is seldom occurred, but due to its less stable, can absorb hernia patch all the time can not be separately as celiocele permanent repair material.For improving the medical effect of hernia patch, reduce patient's misery, the adhesion inhibiting properties and the resistance infection that improve hernia patching material are the targets that scientific research personnel lays siege to always.

Method of electrostatic spinning is fast-developing in recent ten years a kind of simple and effective processing technique of preparing polymer nanocomposite non-weaving cloth.Because gained fibrous material has when high porosity of great specific surface area and surface-to-volume, absorption affinity that material is very strong and good filterability, barrier, adhesion and heat insulating ability etc. have been given, loose structure is conducive to the transmission of nutrient substance simultaneously, therefore electrospinning fibre is widely used in bio-medical field, such as carrying material, tissue engineering bracket material etc. for postoperative adherence preventing material, wound clad material, medicine and gene.

Summary of the invention

The object of the invention is for the support strength existing in existing hernia patch not, easy damaged stomach wall and not resistance to infected defect, thereby provide that a kind of support strength is high, pliability is good for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.

Another object of the present invention is to provide the above-mentioned preparation method for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.

Of the present inventionly for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, comprise the polymer nanofibre film substrate being prepared by method of electrostatic spinning, and the load being prepared by method of electrostatic spinning being connected with described polymer nanofibre film substrate there is the biodegradable high polymer nanometer fiber functional membrane (as shown in Figure 1) of anti-infectives.

According to the present invention, its a kind of embodiment is: described load has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be connected with described polymer nanofibre film substrate, is that described load has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on described polymer nanofibre film substrate.

According to the present invention, its another embodiment is: described load has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be connected with described polymer nanofibre film substrate, to be the described load biodegradable high polymer nanometer fiber functional membrane that has an anti-infectives merge by heat with described polymer nanofibre film substrate is connected, binding agent bonding be connected or sew up be connected.

The thickness of described polymer nanofibre film substrate is preferably 40～150 μ m.

The diameter of the polymer nanofiber in described polymer nanofibre film substrate is preferably 10nm～2000nm.

Described polymer nanofibre film substrate is by not biodegradable, and has good biocompatibility and the good polymeric material of pliability prepares, and the polymer nanofibre film substrate of gained can provide good support strength for the stomach wall of damage.Described polymer is selected from a kind of in polypropylene, politef, polyester, Kynoar.

Described load has the thickness of the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be preferably 10～80 μ m.

Described load has the biodegradable high polymer nanometer fiber of anti-infectives, is anti-infectives is directly scattered in biodegradable macromolecular solution and carries out the biodegradable high polymer nanometer fiber that load that electrostatic spinning obtains has anti-infectives after mixing; Or anti-infectives is joined together with solubilizing agent or cosolvent in biodegradable macromolecular solution and to carry out the biodegradable high polymer nanometer fiber that load that electrostatic spinning obtains has anti-infectives after mixing; Or the anti-infectives that electrostatic spinning is obtained is as core or anti-infectives and natural polymer as core, biodegradable macromolecule has the biodegradable high polymer nanometer fiber of anti-infectives as the load of the nucleocapsid structure of shell; Or the drug delivery system that is embedded with the amphipathic nature block polymer reverse micelle of anti-infectives is scattered in to the biodegradable high polymer nanometer fiber that load in biodegradable high polymer nanometer fiber has anti-infectives.

Described load has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, be to be directly scattered in biodegradable macromolecular solution by anti-infectives, then carrying out together the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber of anti-infectives to obtain; Or be scattered in (adding of solubilizing agent or cosolvent can increase the dissolubility of anti-infectives in solution and the uniformity of dispersion) in biodegradable macromolecular solution by anti-infectives and solubilizing agent or cosolvent, then carrying out together the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber of anti-infectives to obtain; Or be dissolved in separately in solvent or together with natural polymer and be dissolved in solvent by anti-infectives, then with biodegradable macromolecular solution carry out that coaxial electrostatic spinning obtains by anti-infectives as core, biodegradable macromolecule has the biodegradable high polymer nanometer fiber of anti-infectives to obtain as the load of the nucleocapsid structure of shell; Or be scattered in biodegradable macromolecular solution by the drug delivery system that is embedded with the amphipathic nature block polymer reverse micelle of anti-infectives, then carrying out together the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber of anti-infectives to obtain.

Described is directly scattered in biodegradable macromolecular solution by anti-infectives, then carrying out together load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of anti-infectives preferably accounts for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives.

Described by anti-infectives and solubilizing agent or cosolvent, be scattered in biodegradable macromolecular solution, then carrying out together load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of anti-infectives preferably accounts for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, and the content of solubilizing agent or cosolvent preferably accounts for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives.

Described is dissolved in separately in solvent or together with natural polymer and is dissolved in solvent by anti-infectives, then with biodegradable macromolecular solution carry out that coaxial electrostatic spinning obtains by anti-infectives as core, the load that biodegradable macromolecule has the biodegradable high polymer nanometer fiber of anti-infectives to obtain as the load of the nucleocapsid structure of shell has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of the anti-infectives in not containing load that the natural polymer period of the day from 11 p.m. to 1 a.m obtains and have the biodegradable high polymer nanometer fiber functional membrane of anti-infectives preferably accounts for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, the load capacity of the anti-infectives in containing load that the natural polymer period of the day from 11 p.m. to 1 a.m obtains and have the biodegradable high polymer nanometer fiber functional membrane of anti-infectives preferably accounts for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, the content of natural polymer is to account for 0.01%～20% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives.

The described drug delivery system by being embedded with the amphipathic nature block polymer reverse micelle of anti-infectives is scattered in biodegradable macromolecular solution, then carrying out together load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of anti-infectives preferably accounts for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, the content of amphipathic nature block polymer reverse micelle preferably accounts for 0.1%～5% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives.

It is 50nm～2000nm that described load has the diameter of the nanofiber in the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, is preferably 300nm～800nm.

It is to be prepared by the Biodegradable material with suitable degradation cycle that described load has the biodegradable macromolecule in the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, along with biodegradation material degraded in vivo, the anti-infectives of load slowly discharges, effectively prevented the generation of inflammation, and can promote the propagation of collagen to be conducive to patient's rehabilitation.Described biodegradable macromolecule is selected from a kind of in the synthetic macromolecular materials such as polylactic acid, polyglycolic acid, poly (glycolide-lactide), polycaprolactone, Polyethylene Glycol; Or be selected from a kind of in the natural macromolecular materials such as hyaluronic acid, gelatin, chitosan.

Described anti-infectives is water solublity or oil-soluble, is preferably water solublity; Described anti-infectives is macromole or micromolecule, is preferably micromolecule.

Described anti-infectives is selected from a kind of in the anti-microbial type medicines such as cefradine, cefalexin, Roxithromycin, azithromycin, amoxicillin, ciprofloxacin, norfloxacin.

Described solubilizing agent is selected from a kind of in alkylphenol polyoxyethylene, polyoxyethylate amide, Polyethylene Glycol, polyethylene-b-polylactic acid etc.

Described cosolvent is selected from a kind of in organic acid and sodium salt and amide-type etc.; As organic acid and sodium salt thereof are selected from a kind of in benzoic acid, sodium benzoate, salicylic acid, sodium salicylate etc.; Amide-type is selected from a kind of in carbamide, nicotinic acid amide, acetamide etc.

Described amphipathic nature block polymer contains hydrophilic segment and hydrophobic segment simultaneously, hydrophilic segment is selected from a kind of in Polyethylene Glycol (PEG), polyoxyethylene (PEO), polyvinylpyrrolidone (PVP) etc., and hydrophobic segment is selected from a kind of in polylactic acid (PLA), poly lactic coglycolic acid (PLGA), poly-epsilon-caprolactone (PCL), poly-β-benzyl Aspartic Acid (PBLA), poly-benzyl glutamic acid etc.

The present invention is compound by having the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to carry out polymer nanofibre film substrate and load, has realized that stomach wall support strength is high, pliability good, anti-infective is for the preparation of anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.Polymer nanofibre film substrate can keep good support strength, softness, good biocompatibility in long-time; The biodegradable high polymer nanometer fiber functional membrane that load has an anti-infectives, along with the degraded of material can progressively discharge anti-infectives, has effectively prevented the generation of post-operative infection and inflammation, has reduced patient's misery.

Preparation method for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation of the present invention has following several:

The technical scheme of method 1 comprises the following steps:

(1) prepared polymer electrostatic spinning solution:

The polymer dissolution that will carry out electrostatic spinning is in organic solvent (temperature of generally selecting dissolving is 20～80 ℃) and stir (the general time of stirring is 3～12 hours), obtains polymer electrospun solution; Preferably, the volumetric concentration of described polymer electrospun solution is 50～500mg/mL;

(2) by electrostatic spinning, prepare polymer nanofibre film substrate:

The polymer electrospun solution that step (1) is obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtains polymer nanofibre film substrate; The condition of described electrostatic spinning can adopt prior art, as the feeding rate of adjusting polymer electrospun solution is 3～100 μ L/min, distance between the spinning head of charging gear (as adopted 5# syringe needle) and the metal receiving system of ground connection is preferably 10～20cm, voltage is preferably 10～30kV, more preferably 15～25kV;

(3) the biodegradable polymer electrostatic spinning solution of preparation medicine carrying:

The biodegradable macromolecule dissolution that will carry out electrostatic spinning (temperature of generally selecting dissolving is 20～60 ℃) stir (general stir time be 3～12 hours) in organic solvent, obtain biodegradable macromolecular solution, then anti-infectives is directly scattered in to (temperature of generally selecting is 20～60 ℃) in biodegradable macromolecular solution, (the general time of stirring is 3～12 hours) stirs, anti-infectives is dispersed in biodegradable macromolecule, obtain the biodegradable polymer electrostatic spinning solution of medicine carrying, preferably, the volumetric concentration of described biodegradable macromolecule in electrostatic spinning solution is 50～500mg/mL, the volumetric concentration of described anti-infectives in electrostatic spinning solution is 1～10mg/mL, or anti-infectives and solubilizing agent or cosolvent are scattered in to (temperature of generally selecting is 20～60 ℃) in biodegradable macromolecular solution, (the general time of stirring is 3～12 hours) stirs, anti-infectives is dispersed in biodegradable macromolecule, obtains the biodegradable polymer electrostatic spinning solution of medicine carrying, preferably, the volumetric concentration of described biodegradable macromolecule in electrostatic spinning solution is 50～500mg/mL, the volumetric concentration of described anti-infectives in electrostatic spinning solution is 1～10mg/mL, and described solubilizing agent or the cosolvent volumetric concentration in the biodegradable polymer electrostatic spinning solution of medicine carrying is 1～10mg/mL,

(4) have the biodegradable high polymer nanometer fiber functional membrane of anti-infectives compound polymer nanofibre film substrate and load:

On the metal connection device of the ground connection when polymer nanofibre film substrate directly step (2) being made is placed in and carries out electrostatic spinning, then the biodegradable polymer electrostatic spinning solution of medicine carrying step (3) being obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, and making to carry out the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on polymer nanofibre film substrate; Or

The biodegradable polymer electrostatic spinning solution of medicine carrying that step (3) is obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtains the biodegradable high polymer nanometer fiber functional membrane that load has anti-infectives; Then polymer nanofibre film substrate step (2) being made with carry out after load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be superimposed carrying out heat fusion by heating, or by binding agent, undertaken bondingly, or be connected by modes such as stitchings;

The condition of described electrostatic spinning can adopt prior art, as the feeding rate of adjusting the biodegradable polymer electrostatic spinning solution of medicine carrying is 3～100 μ L/min, distance between the spinning head of charging gear (as adopted 5# syringe needle) and the metal connection device of ground connection is preferably 10～20cm, voltage is preferably 10～30kV, 13～25kV more preferably, also 13～20kV more preferably;

(5) composite electrostatic spinning nano fibrous membrane step (4) being obtained is placed (the general time of placing is 24～72 hours) in vacuum drying oven, thoroughly remove remaining organic solvent, can make for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.

The technical scheme of method 2 comprises the following steps:

(1) prepared polymer electrostatic spinning solution:

(2) by electrostatic spinning, prepare polymer nanofibre film substrate:

The polymer electrospun solution that step (1) is obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtains polymer nanofibre film substrate; The condition of described electrostatic spinning can adopt prior art, as the feeding rate of adjusting polymer electrospun solution is 3～100 μ L/min, distance between the spinning head of charging gear (as adopted 5# syringe needle) and the metal connection device of ground connection is preferably 10～20cm, voltage is preferably 10～30kV, more preferably 15～25kV;

(3) prepare biodegradable polymer electrostatic spinning solution:

The biodegradable macromolecule dissolution that will carry out electrostatic spinning is in organic solvent (temperature of generally selecting dissolving is 20～80 ℃) and stir (the general time of stirring is 3～12 hours), obtains biodegradable polymer electrostatic spinning solution; Preferably, the volumetric concentration of described biodegradable macromolecule in electrostatic spinning solution is 50～500mg/mL;

(4) preparation anti-infectives solution:

Anti-infectives that will load is dissolved in separately (temperature of generally selecting dissolving is 20～60 ℃) stir (the general time of stirring is 1～4 hour) in solvent, and preferably, obtaining volumetric concentration is the anti-infectives solution of 1～10mg/mL; Or anti-infectives that will load is dissolved in (temperature of generally selecting dissolving is 20～60 ℃) stir (the general time of stirring is 1～4 hour) in solvent together with natural polymer, preferably, the volumetric concentration that obtains anti-infectives is 1～10mg/mL, the anti-infectives solution that the volumetric concentration of natural polymer is 1～100mg/mL;

(5) have the biodegradable high polymer nanometer fiber functional membrane of anti-infectives compound polymer nanofibre film substrate and load:

On the metal connection device of the ground connection when polymer nanofibre film substrate directly step (2) being made is placed in and carries out coaxial electrostatic spinning, then the anti-infectives solution that biodegradable polymer electrostatic spinning solution step (3) being obtained and step (4) obtain is injected into respectively in two liquid storage containers of charging gear of electrostatic spinning apparatus, the liquid storage container that is mounted with anti-infectives solution is connected with the inner tube of a coaxial spinning head by feeder sleeve, the liquid storage container that is mounted with biodegradable polymer electrostatic spinning solution is connected with the outer tube of described coaxial spinning head by feeder sleeve, the pump of opening charging gear carries out coaxial electrostatic spinning, make to carry out that coaxial electrostatic spinning obtains obtains anti-infectives as core, biodegradable macromolecule has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on polymer nanofibre film substrate as the load of the nucleocapsid structure of shell, or

The anti-infectives solution that the biodegradable polymer electrostatic spinning solution that step (3) is obtained and step (4) obtain is injected into respectively in two liquid storage containers of charging gear of electrostatic spinning apparatus, the liquid storage container that is mounted with anti-infectives solution is connected with the inner tube of a coaxial spinning head by feeder sleeve, and the liquid storage container that is mounted with biodegradable polymer electrostatic spinning solution is connected with the outer tube of described coaxial spinning head by feeder sleeve; The pump of opening charging gear carries out coaxial electrostatic spinning, obtains anti-infectives as core, and biodegradable macromolecule has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives as the load of the nucleocapsid structure of shell; Then polymer nanofibre film substrate step (2) being made with carry out anti-infectives that coaxial electrostatic spinning obtains as core, after biodegradable macromolecule has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be superimposed as the load of shell, by heating, carrying out heat merges, or by binding agent, undertaken bondingly, or be connected by modes such as stitchings;

The condition of described coaxial electrostatic spinning can adopt prior art, as the distance between the metal connection device of coaxial spinning head and ground connection is preferably 10～20cm, voltage is preferably 10～30kV, feeding rate is 3～100 μ L/min, adjust the feeding rate of two liquid storage containers, the feed volume ratio that makes biodegradable polymer electrostatic spinning solution and anti-infectives solution is the adjustment that 7:1～3:1(passes through voltage and feeding rate, can obtain the fiber of different-diameter and core-shell diameter ratio);

(6) composite electrostatic spinning nano fibrous membrane step (5) being obtained is placed (the general time of placing is 24～72 hours) in vacuum drying oven, thoroughly remove remaining organic solvent, can make for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.

The technical scheme of method 3 comprises the following steps:

(1) prepared polymer electrostatic spinning solution:

(2) by electrostatic spinning, prepare polymer nanofibre film substrate:

(3) prepare biodegradable polymer electrostatic spinning solution:

(4) prepare drug delivery system:

Anti-infectives is joined in the solution that contains amphipathic nature block polymer reverse micelle obtaining while preparing amphipathic nature block polymer reverse micelle, obtain being embedded with the drug delivery system of the amphipathic nature block polymer reverse micelle of anti-infectives; Wherein, the content of anti-infectives be account for the amphipathic nature block polymer reverse micelle that is embedded with anti-infectives drug delivery system gross weight 5%～50%;

On the metal connection device of the ground connection when polymer nanofibre film substrate directly step (2) being made is placed in and carries out electrostatic spinning, the drug delivery system of the amphipathic nature block polymer reverse micelle that is embedded with anti-infectives then step (4) being obtained is dispersed in the biodegradable polymer electrostatic spinning solution that step (3) obtains, fully stir (the general time of stirring is 4～12 hours), obtain electrostatic spinning mixed solution; Wherein, the volumetric concentration of described biodegradable macromolecule in electrostatic spinning mixed solution is 50～500mg/mL, and the volumetric concentration of the described amphipathic nature block polymer reverse micelle that is embedded with anti-infectives in electrostatic spinning mixed solution is 1～50mg/mL; Electrostatic spinning mixed solution is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, making to carry out the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on polymer nanofibre film substrate; Or

The drug delivery system of the amphipathic nature block polymer reverse micelle that is embedded with anti-infectives that step (4) is obtained is dispersed in the biodegradable polymer electrostatic spinning solution that step (3) obtains, fully stir (the general time of stirring is 4～12 hours), obtain electrostatic spinning mixed solution; Wherein, the volumetric concentration of described biodegradable macromolecule in electrostatic spinning mixed solution is 50～500mg/mL, and the volumetric concentration of the described amphipathic nature block polymer reverse micelle that is embedded with anti-infectives in electrostatic spinning mixed solution is 1～50mg/mL; Electrostatic spinning mixed solution is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtain the biodegradable high polymer nanometer fiber functional membrane that load has anti-infectives; Then polymer nanofibre film substrate step (2) being made with carry out after load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be superimposed carrying out heat fusion by heating, or by binding agent, undertaken bondingly, or be connected by modes such as stitchings;

The condition of described electrostatic spinning can adopt prior art, as the feeding rate of adjusting electrostatic spinning mixed solution is 3～100 μ L/min, distance between the spinning head of charging gear (as adopted 5# syringe needle) and the metal connection device of ground connection is preferably 10～20cm, voltage is preferably 10～30kV, 13～25kV more preferably, also 13～20kV more preferably;

Step (1) in the technical scheme of method 1,2,3 can be selected from acetone, oxolane, chloroform, dichloromethane, chloroform, N with the organic solvent in step (3), one or more in dinethylformamide, N,N-dimethylacetamide isopolarity organic solvent.

Solvent described in step in the technical scheme of method 2 (4) can be selected from one or more in water, acetone, oxolane, chloroform, dichloromethane, chloroform, DMF, N,N-dimethylacetamide etc.In the anti-infectives solution of preparation, can further add natural macromolecular material to increase the stability of coaxial electrostatic spinning; Preferably, the volumetric concentration of described natural macromolecular material in described anti-infectives solution is 1～100mg/mL.A kind of in the optional self-induced transparency matter acid of described natural macromolecular material, gelatin, chitosan etc.

Described metal receiving system can be flat board or cylinder, on it, can be covered with aluminium foil or tinfoil.

The diameter of the polymer nanofiber in described polymer nanofibre film substrate is 10nm～2000nm.

Described polymer is selected from a kind of in polypropylene, politef, polyester, Kynoar.

The described load obtaining in the technical scheme of method 1 has the load in the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to have the diameter of the biodegradable high polymer nanometer fiber of anti-infectives to be preferably 50～2000nm, more preferably 300～800nm.

The described load obtaining in the technical scheme of method 2 has the load in the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to have the diameter of the biodegradable high polymer nanometer fiber of anti-infectives to be preferably 300～2000nm.

The described load obtaining in the technical scheme of method 3 has the load in the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to have the diameter of the biodegradable high polymer nanometer fiber of anti-infectives to be preferably 50～2000nm, more preferably 300～800nm.

Described biodegradable macromolecule is selected from a kind of in the synthetic macromolecular materials such as polylactic acid, polyglycolic acid, poly (glycolide-lactide), polycaprolactone, Polyethylene Glycol, or is selected from a kind of in the natural macromolecular materials such as hyaluronic acid, gelatin, chitosan.

The preparation of described amphipathic nature block polymer reverse micelle can adopt existing technology of preparing, as document that can reference has: 1, Journal of Polymer Science:Part A:Polymer Chemistry48 (2010): 2855-2861.2、International?Journal?of?Pharmaceutics398(2010):204-209。3、Pharmaceutical?Research27(2010):1861-1868。4、Acta?Biomaterialia5(2009):3112-3121。

In described drug delivery system, also can comprise micelle, microsphere and intelligent gel etc.

Of the present invention have postoperative infection for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, soft, good biocompatibility, and can provide for a long time enough mechanical properties, feature with long term maintenance stomach wall support strength, can be widely used in herniorrhaphy, the shape of described hernia patch can be carried out cutting with wound.Hernia patch of the present invention, after implant into body, in repairing hernia, can effectively reduce the inflammatory reaction that postoperative infection causes, reduces patient's misery.

The present invention compared with prior art, has the following advantages: (1) adopts nano-scale fiber, and itself is splendid with the compatibility of organism, and reaction is difficult for causing inflammation; (2) electrostatic spinning nano fibrous membrane substrate softness and mechanical property are good, can not cause the damage of internal organs, and the support of stomach wall can be provided for a long time, make internal organs can be fixed on post-operative recovery position; (3) organic solvent volatilization in electrostatic spinning process, after sufficient vacuum drying, does not have chemical agent residue, avoids the injury to human body; (4) adopting medicine-carried system to carry out the load that electrospinning obtains has the electrostatic spinning nano fiber functional membrane of anti-infectives to have suitable degradation speed, degraded along with material, anti-infectives discharges gradually, can effectively prevent postoperative infection and the caused inflammation of wound contamination.

Accompanying drawing explanation

Fig. 1. the schematic diagram for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation of the present invention.

Fig. 2. scanning electron microscope (SEM) photo of the electrostatic spinning nano fibrous membrane substrate of the embodiment of the present invention 1.

Fig. 3. the load of the embodiment of the present invention 1 has scanning electron microscope (SEM) photo of electrostatic spinning nano fiber functional membrane of the poly (glycolide-lactide) of amoxicillin.

Fig. 4. the embodiment of the present invention 5 carry out transmission electron microscope (TEM) photo that the load with nucleocapsid structure that coaxial electrostatic spinning obtains has the polylactic acid nano fiber of cefradine.

Fig. 5. transmission electron microscope (TEM) photo of the medicine carrying reverse micelle of the embodiment of the present invention 6.

The specific embodiment

Embodiment 1

(1) Kynoar is dissolved in the mixed solvent of DMF (DMF) and acetone (Acetone), the volume ratio of the DMF/Acetone in its mixed solvent is 5/5; In temperature, be at 50 ℃, to stir 12 hours, Kynoar is sufficiently uniformly dissolved, making volumetric concentration is the Kynoar electrostatic spinning solution of 150mg/mL;

(2) Kynoar electrostatic spinning solution step (1) being obtained is injected in the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, syringe is placed in to propeller, connect board joint receiving apparatus that the earth's surface is covered with aluminium foil or tinfoil be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 40 μ L/min, adjustment voltage is 15kV, Kynoar electrostatic spinning liquid ejects nanofiber under the effect of electrostatic field, fall within the surface of described board joint receiving apparatus, obtain polyvinylidene fluoride nanometer fibrous membrane substrate, the thickness of described Kynoar electrostatic spinning nano fibrous membrane substrate is 45 μ m, fibre diameter be 500nm～800nm(as shown in Figure 2),

(3) aids drug amoxicillin and Biodegradable high-molecular poly (glycolide-lactide) are dissolved in to N, in dinethylformamide, at 40 ℃, stir 12 hours, make amoxicillin fully dissolve and mix homogeneously with poly (glycolide-lactide), obtain being loaded with the poly (glycolide-lactide) electrostatic spinning solution of amoxicillin, wherein, the volumetric concentration of described amoxicillin in electrostatic spinning liquid is 10mg/mL, and the volumetric concentration of poly (glycolide-lactide) in electrostatic spinning solution is 400mg/mL;

(4) the resulting poly (glycolide-lactide) electrostatic spinning solution that is loaded with amoxicillin of step (3) is placed in to the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, connect board joint receiving apparatus that the earth's surface is covered with the prepared Kynoar electrostatic spinning nano of step (2) fibrous membrane substrate be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 50 μ L/min, adjustment voltage is 20kV, the poly (glycolide-lactide) electrostatic spinning liquid that is loaded with amoxicillin sprays and becomes nanofiber under the effect of electrostatic field, and fall within on the surface of described polyvinylidene fluoride nanometer fibrous membrane substrate, obtaining load has the poly (glycolide-lactide) functional membrane of amoxicillin, and make composite electrostatic spinning nano fibrous membrane (SEM photo as shown in Figure 3), the thickness of the described poly (glycolide-lactide) functional membrane that is loaded with amoxicillin is 45 μ m, and fibre diameter is 600nm,

Or the poly (glycolide-lactide) electrostatic spinning solution that is loaded with amoxicillin that step (3) is obtained is injected in the charging gear of electrostatic spinning apparatus, and carry out electrostatic spinning according to above-mentioned condition, obtain the poly (glycolide-lactide) functional membrane that load has amoxicillin; Then Kynoar electrostatic spinning nano fibrous membrane substrate step (2) being made with carry out after load that electrostatic spinning obtains has the poly (glycolide-lactide) functional membrane of amoxicillin to be superimposed carrying out heat fusion by heating, or undertaken bonding by binding agent, or be connected by the mode of sewing up, make composite electrostatic spinning nano fibrous membrane; The thickness of the described poly (glycolide-lactide) functional membrane that is loaded with amoxicillin is 45 μ m, and fibre diameter is 600nm;

(5) composite electrostatic spinning nano fibrous membrane step (4) being obtained is placed 48 hours in vacuum drying oven, thoroughly removes remaining organic solvent, can make for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.

Embodiment 2

(1) polyethylene terephthalate (PET) is dissolved in the mixed solvent of trifluoroacetic acid and dichloromethane, the volume ratio of its mixed solvent is 5/5; In temperature, be at 50 ℃, to stir 12 hours, PET is sufficiently uniformly dissolved, making volumetric concentration is the PET electrostatic spinning solution of 150mg/mL;

(2) PET electrostatic spinning solution step (1) being obtained is injected in the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, syringe is placed in to propeller, connect board joint receiving apparatus that the earth's surface is covered with aluminium foil or tinfoil be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 7 μ L/min, adjustment voltage is 25kV, PET electrostatic spinning liquid ejects nanofiber under the effect of electrostatic field, fall within the surface of described board joint receiving apparatus, obtain PET nanofiber film substrate, the thickness of described PET electrostatic spinning nano fibrous membrane substrate is 45 μ m, fibre diameter is 300nm～500nm,

(3) aids drug cefradine is dissolved in to N with after a small amount of Polyethylene Glycol (or salicylic acid) mixes, in dinethylformamide, under room temperature, stir 4 hours, make it dispersed, then add Biodegradable high-molecular poly (glycolide-lactide), at 40 ℃, stir 12 hours, it is fully dissolved also dispersed, obtain being loaded with the poly (glycolide-lactide) electrostatic spinning solution of cefradine, wherein, the volumetric concentration of described cefradine in the described poly (glycolide-lactide) electrostatic spinning solution that is loaded with cefradine is 1mg/mL, the volumetric concentration of described Polyethylene Glycol (or salicylic acid) in the described poly (glycolide-lactide) electrostatic spinning solution that is loaded with cefradine is 10mg/mL, it is 400mg/mL that described poly (glycolide-lactide) has the volumetric concentration in the poly (glycolide-lactide) electrostatic spinning solution of cefradine in described load,

(4) the resulting poly (glycolide-lactide) electrostatic spinning solution that is loaded with cefradine of step (3) is placed in to the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, connect board joint receiving apparatus that the earth's surface is covered with the prepared PET electrostatic spinning nano of step (2) fibrous membrane substrate be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 40 μ L/min, adjustment voltage is 18kV, the poly (glycolide-lactide) electrostatic spinning liquid that is loaded with cefradine sprays and becomes nanofiber under the effect of electrostatic field, and fall within on the surface of described PET nanofiber film substrate, obtain being loaded with the poly (glycolide-lactide) functional membrane of cefradine, and make composite electrostatic spinning nano fibrous membrane, the thickness of the described poly (glycolide-lactide) functional membrane that is loaded with cefradine is 45 μ m, and fibre diameter is 500nm,

Embodiment 3

(1) Kynoar is dissolved in the mixed solvent of DMF (DMF) and acetone (Acetone), the volume ratio of the DMF/Acetone in its mixed solvent is 7/3; In temperature, be at 50 ℃, to stir 12 hours, Kynoar is sufficiently uniformly dissolved, making volumetric concentration is the Kynoar electrostatic spinning solution of 150mg/mL;

(2) Kynoar electrostatic spinning solution step (1) being obtained is injected in the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, syringe is placed in to propeller, connect board joint receiving apparatus that the earth's surface is covered with aluminium foil or tinfoil be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 25 μ L/min, adjustment voltage is 15kV, Kynoar electrostatic spinning liquid ejects nanofiber under the effect of electrostatic field, fall within the surface of described board joint receiving apparatus, obtain polyvinylidene fluoride nanometer fibrous membrane substrate, the thickness of described Kynoar electrostatic spinning nano fibrous membrane substrate is 50 μ m, fibre diameter is 300nm～800nm,

(3) aids drug cefradine is dissolved in to N with after a small amount of Polyethylene Glycol mixes, in dinethylformamide, under room temperature, stir 4 hours, make it dispersed, then add Biodegradable high-molecular poly (glycolide-lactide), at 40 ℃, stir 12 hours, it is fully dissolved also dispersed, obtain being loaded with the poly (glycolide-lactide) electrostatic spinning solution of cefradine, wherein, the volumetric concentration of described cefradine in the described poly (glycolide-lactide) electrostatic spinning solution that is loaded with cefradine is 1mg/mL, the volumetric concentration of described Polyethylene Glycol in the described poly (glycolide-lactide) electrostatic spinning solution that is loaded with cefradine is 10mg/mL, it is 400mg/mL that described poly (glycolide-lactide) has the volumetric concentration in the poly (glycolide-lactide) electrostatic spinning solution of cefradine in described load,

(4) the resulting poly (glycolide-lactide) electrostatic spinning solution that is loaded with cefradine of step (3) is placed in to the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, the board joint receiving apparatus of ground connection be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 40 μ L/min, adjustment voltage is 18kV, the poly (glycolide-lactide) electrostatic spinning liquid that is loaded with cefradine sprays and becomes nanofiber under the effect of electrostatic field, and fall within on board joint receiving apparatus surface, obtain being loaded with the poly (glycolide-lactide) functional membrane of cefradine, the thickness of the described poly (glycolide-lactide) functional membrane that is loaded with cefradine is 45 μ m, fibre diameter is 500nm, the load that the Kynoar electrostatic spinning nano fibrous membrane substrate that step (2) is made and electrostatic spinning obtain has the poly (glycolide-lactide) functional membrane of cefradine to be superimposed to be placed on carries out hot pressing in film laminator, the temperature of adjusting press mold is 150 ℃, the pressure of press mold is 0.2MPa, the time of press mold is 10 minutes, makes composite electrostatic spinning nano fibrous membrane, also the load that the Kynoar electrostatic spinning nano fibrous membrane substrate that mode that is can be by binding agent bonding or that sew up makes step (2) obtains with electrostatic spinning has the poly (glycolide-lactide) functional membrane of cefradine to be connected, and makes composite electrostatic spinning nano fibrous membrane,

Embodiment 4

(1) Kynoar is dissolved in the mixed solvent of DMF (DMF) and acetone (Acetone), the volume ratio of the DMF/Acetone in its mixed solvent is 3/7; In temperature, be at 50 ℃, to stir 12 hours, Kynoar is sufficiently uniformly dissolved, making volumetric concentration is the Kynoar electrostatic spinning solution of 150mg/mL;

(2) Kynoar electrostatic spinning solution step (1) being obtained is injected in the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, syringe is placed in to propeller, connect board joint receiving apparatus that the earth's surface is covered with aluminium foil or tinfoil be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 70 μ L/min, adjustment voltage is 25kV, Kynoar electrostatic spinning liquid ejects nanofiber under the effect of electrostatic field, fall within the surface of described board joint receiving apparatus, obtain polyvinylidene fluoride nanometer fibrous membrane substrate, the thickness of described Kynoar electrostatic spinning nano fibrous membrane substrate is 80 μ m, fibre diameter is 500nm～1500nm,

(3) Biodegradable high-molecular polylactic acid is dissolved in DMF, at 50 ℃, stirs 12 hours, it is fully dissolved, make the shell solution for coaxial electrostatic spinning; The volumetric concentration of described polylactic acid in described shell solution is 400mg/mL;

(4) aids drug cefradine is dissolved in distilled water, stirs and it was fully dissolved in 4 hours under room temperature, make the inner core solution for coaxial electrostatic spinning, wherein, the volumetric concentration of described cefradine in described inner core solution is 10mg/mL;

(5) the polyvinylidene fluoride nanometer fibrous membrane substrate directly step (2) being made is placed on the grounded metal receiving system that carries out coaxial electrostatic spinning, then the cefradine solution that polylactic acid electrostatic spinning solution step (3) being obtained and step (4) obtain is injected into respectively in two liquid storage containers of charging gear of electrostatic spinning apparatus, the liquid storage container that is mounted with cefradine solution is connected with the inner tube of a coaxial spinning head by feeder sleeve, and the liquid storage container that is mounted with polylactic acid solution is connected with the outer tube of described coaxial spinning head by feeder sleeve; Adjusting described grounded metal receiving system is 15cm with the distance between coaxial spinning head, open the pump of charging gear, the propelling speed of adjusting inner core solution is 10 μ L/min, the propelling speed of shell solution is 50 μ L/min, adjusting voltage is that 14kV carries out coaxial electrostatic spinning, making to carry out the cefradine that coaxial electrostatic spinning obtains has the polylactic acid nano fiber functional membrane of cefradine to be directly molded on polyvinylidene fluoride nanometer fibrous membrane substrate as core, polylactic acid as the load of the nucleocapsid structure of shell, obtains composite electrostatic spinning nano fibrous membrane; The thickness of the described polylactic acid nano fiber film that is loaded with cefradine is 45 μ m, and fibre diameter is about 800nm;

(6) composite electrostatic spinning nano fibrous membrane step (5) being obtained is placed 48 hours in vacuum drying oven, thoroughly removes remaining organic solvent, can make for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.

Embodiment 5

(2) Kynoar electrostatic spinning solution step (1) being obtained is injected in the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, syringe is placed in to propeller, connect board joint receiving apparatus that the earth's surface is covered with aluminium foil or tinfoil be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 50 μ L/min, adjustment voltage is 25kV, Kynoar electrostatic spinning liquid ejects nanofiber under the effect of electrostatic field, fall within the surface of described board joint receiving apparatus, obtain polyvinylidene fluoride nanometer fibrous membrane substrate, the thickness of described Kynoar electrostatic spinning nano fibrous membrane substrate is 50 μ m, fibre diameter is 500nm～1000nm,

(4) aids drug cefradine and a small amount of hyaluronic acid are dissolved in distilled water, under room temperature, stir and they were fully dissolved in 4 hours, make the inner core solution for coaxial electrostatic spinning, wherein, the volumetric concentration of described cefradine in described inner core solution is 10mg/mL, and the volumetric concentration of described hyaluronic acid in described inner core solution is 70mg/mL;

(5) the polyvinylidene fluoride nanometer fibrous membrane substrate directly step (2) being made is placed on the grounded metal receiving system that carries out coaxial electrostatic spinning, then the cefradine solution that polylactic acid electrostatic spinning solution step (3) being obtained and step (4) obtain is injected into respectively in two liquid storage containers of charging gear of electrostatic spinning apparatus, the liquid storage container that is mounted with cefradine solution is connected with the inner tube of a coaxial spinning head by feeder sleeve, and the liquid storage container that is mounted with polylactic acid solution is connected with the outer tube of described coaxial spinning head by feeder sleeve; Adjusting described grounded metal receiving system is 15cm with the distance between coaxial spinning head, open the pump of charging gear, the propelling speed of adjusting inner core solution is 10 μ L/min, the propelling speed of shell solution is 50 μ L/min, adjusting voltage is that 14kV carries out coaxial electrostatic spinning, making to carry out the cefradine that coaxial electrostatic spinning obtains has the polylactic acid nano fiber functional membrane of cefradine to be directly molded on polyvinylidene fluoride nanometer fibrous membrane substrate as core, polylactic acid as the load of the nucleocapsid structure of shell, obtains composite electrostatic spinning nano fibrous membrane; The thickness of the described polylactic acid nano fiber film that is loaded with cefradine is 45 μ m, and fibre diameter is about 800nm, the load with nucleocapsid structure have cefradine polylactic acid nano fiber transmission electron microscope picture as shown in Figure 4;

Or the cefradine solution that obtains of the polylactic acid electrostatic spinning solution that step (3) is obtained and step (4) is injected into respectively in two liquid storage containers of charging gear of electrostatic spinning apparatus, the liquid storage container that is mounted with cefradine solution is connected with the inner tube of a coaxial spinning head by feeder sleeve, and the liquid storage container that is mounted with polylactic acid electrostatic spinning solution is connected with the outer tube of described coaxial spinning head by feeder sleeve; The pump of opening charging gear, carries out coaxial electrostatic spinning according to above-mentioned condition, obtains cefradine as core, and the load of the quiet nucleocapsid structure as shell of polylactic acid has the polylactic acid nano fiber functional membrane of cefradine; Then polyvinylidene fluoride nanometer fibrous membrane substrate step (2) being made with carry out cefradine that coaxial electrostatic spinning obtains as core, after the load of the quiet nucleocapsid structure as shell of polylactic acid has the polylactic acid nano fiber functional membrane of cefradine to be superimposed, by heating, carrying out heat merges, or undertaken bonding by binding agent, or be connected by the mode of sewing up, obtain composite electrostatic spinning nano fibrous membrane; The thickness of the described polylactic acid nano fiber film that is loaded with cefradine is 45 μ m, and fibre diameter is about 800nm, the load with nucleocapsid structure have cefradine polylactic acid nano fiber transmission electron microscope picture as shown in Figure 4;

Embodiment 6

(1) Kynoar is dissolved in to N, in the mixed solvent of dinethylformamide and acetone, its mixed solvent volume ratio is DMF/Acetone=3/7, and this mixture is stirred 12 hours at 50 ℃, it is fully dissolved, make Kynoar electrostatic spinning solution; The volumetric concentration of described Kynoar in Kynoar electrostatic spinning solution is 150mg/mL;

(2) Kynoar electrostatic spinning solution step (1) being obtained is injected in the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, syringe is placed in to propeller, connect board joint receiving apparatus that the earth's surface is covered with aluminium foil or tinfoil be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 5 μ L/min, adjustment voltage is 20kV, Kynoar electrostatic spinning liquid ejects nanofiber under the effect of electrostatic field, fall within the surface of described board joint receiving apparatus, obtain polyvinylidene fluoride nanometer fibrous membrane substrate, the thickness of described Kynoar electrostatic spinning nano fibrous membrane substrate is 100 μ m, fibre diameter is 200nm～500nm,

(3) Biodegradable high-molecular polylactic acid is dissolved in DMF, at 40 ℃, stirs 12 hours, it is fully dissolved, obtain polylactic acid electrostatic spinning solution; The volumetric concentration of described polylactic acid in described electrostatic spinning solution is 200mg/mL;

(4) adopt amphipathic block copolymer polyethylene-b-polylactic acid (PELA) to prepare micro-crosslinked medicine carrying reverse micelle, 0.375gPELA is joined in 50mL there-necked flask, add 25mL chloroform to stir, add the triethylamine 4.44 μ L with amount of substances such as PELA, there-necked flask is placed in to ice-water bath, slowly drip methacrylic chloride 4.3 μ L, carry out functional group reactions, introduce terminal double bond, after dropwising, take out there-necked flask, under room temperature, stir and spend the night, reactant liquor is concentrated with revolving steaming instrument, then use ether sedimentation, obtain polymer powder, polymer powder is dissolved in 25mLDMF again, adding cefradine (5mg/ml) to wrap carries, add photosensitizer benzophenone (polymer quality 1%) 3.75mg, after fully dissolving, sample is placed in to 3～5 seconds initiation shells of irradiation under UV lamp (290～360nm) to be cross-linked, make medicine carrying reverse micelle (as shown in Figure 5), wherein, the diameter Distribution of described medicine carrying reverse micelle is 300～800nm,

(5) the drug delivery system of the PELA reverse micelle that is embedded with cefradine step (4) being obtained is dispersed in the polylactic acid electrostatic spinning solution that step (3) obtains, under 40 ℃ of conditions, stir 12 hours, make its mix homogeneously, obtain electrostatic spinning mixed solution, electrostatic spinning mixed solution is placed in to the 5mL syringe of electrostatic spinning apparatus, adopt 5# syringe needle, connect board joint receiving apparatus that the earth's surface is covered with the prepared Kynoar electrostatic spinning nano of step (2) fibrous membrane substrate be positioned at 5# syringe needle under, adjusting described board joint receiving apparatus and the distance between 5# syringe needle is 15cm, adjusting and advancing speed is 50 μ L/min, adjustment voltage is 13kV, the polylactic acid electrostatic spinning liquid that is loaded with cefradine sprays and becomes nanofiber under the effect of electrostatic field, and fall within on the surface of described polyvinylidene fluoride nanometer fibrous membrane substrate, obtain being loaded with the poly (glycolide-lactide) functional membrane of cefradine, and make composite electrostatic spinning nano fibrous membrane, the thickness of the described polylactic acid functional membrane that is loaded with cefradine is 45 μ m, and fibre diameter is 600nm,

Although in conjunction with specific embodiments the present invention has been carried out to above-mentioned explanation, the invention is not restricted to embodiment described above, for the improvement that above-mentioned technology is replaced on an equal basis or combined, all fall within the scope of protection of present invention.

Claims

1. one kind for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: described hernia patch comprises the polymer nanofibre film substrate being prepared by method of electrostatic spinning, and the load being prepared by method of electrostatic spinning being connected with described polymer nanofibre film substrate has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives.

2. according to claim 1 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: described load has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be connected with described polymer nanofibre film substrate, is that described load has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on described polymer nanofibre film substrate; Or the described load biodegradable high polymer nanometer fiber functional membrane that has an anti-infectives merge by heat with described polymer nanofibre film substrate be connected, binding agent bonding be connected or sew up be connected.

3. according to claim 1 and 2 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: the thickness of described polymer nanofibre film substrate is 40～150 μ m.

4. according to claim 3 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: the diameter of the polymer nanofiber in described polymer nanofibre film substrate is 10nm～2000nm.

According to described in claim 1,2 or 4 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: described polymer is selected from a kind of in polypropylene, politef, polyester, Kynoar.

6. according to claim 1 and 2 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: described load has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, be to be directly scattered in biodegradable macromolecular solution by anti-infectives, then carrying out together the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber of anti-infectives to obtain; Or be scattered in biodegradable macromolecular solution by anti-infectives and solubilizing agent or cosolvent, then carrying out together the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber of anti-infectives to obtain; Or be dissolved in separately in solvent or together with natural polymer and be dissolved in solvent by anti-infectives, then with biodegradable macromolecular solution carry out that coaxial electrostatic spinning obtains by anti-infectives as core, biodegradable macromolecule has the biodegradable high polymer nanometer fiber of anti-infectives to obtain as the load of the nucleocapsid structure of shell; Or be scattered in biodegradable macromolecular solution by the drug delivery system that is embedded with the amphipathic nature block polymer reverse micelle of anti-infectives, then carrying out together the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber of anti-infectives to obtain.

7. according to claim 6 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: described is directly scattered in biodegradable macromolecular solution by anti-infectives, then carrying out together load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of anti-infectives is to account for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives;

Described by anti-infectives and solubilizing agent or cosolvent, be scattered in biodegradable macromolecular solution, then carrying out together load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of anti-infectives is to account for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, and the content of solubilizing agent or cosolvent is to account for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives;

Described is dissolved in separately in solvent or together with natural polymer and is dissolved in solvent by anti-infectives, then with biodegradable macromolecular solution carry out that coaxial electrostatic spinning obtains by anti-infectives as core, the load that biodegradable macromolecule has the biodegradable high polymer nanometer fiber of anti-infectives to obtain as the load of the nucleocapsid structure of shell has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of the anti-infectives in not containing load that the natural polymer period of the day from 11 p.m. to 1 a.m obtains and have the biodegradable high polymer nanometer fiber functional membrane of anti-infectives is to account for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, the load capacity of the anti-infectives in containing load that the natural polymer period of the day from 11 p.m. to 1 a.m obtains and have the biodegradable high polymer nanometer fiber functional membrane of anti-infectives is to account for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, the content of natural polymer is to account for 0.01%～20% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives,

The described drug delivery system by being embedded with the amphipathic nature block polymer reverse micelle of anti-infectives is scattered in biodegradable macromolecular solution, then carrying out together load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives, wherein, the load capacity of anti-infectives is to account for 0.01%～2% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives, the content of amphipathic nature block polymer reverse micelle is to account for 0.1%～5% of biodegradable high polymer nanometer fiber functional membrane gross weight that load has anti-infectives.

8. according to claim 6 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: it is 50nm～2000nm that described load has the diameter of the biodegradable high polymer nanometer fiber of anti-infectives.

According to described in claim 1,2,7 or 8 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: described biodegradable macromolecule is selected from a kind of in polylactic acid, polyglycolic acid, poly (glycolide-lactide), polycaprolactone, Polyethylene Glycol, hyaluronic acid, gelatin, chitosan.

According to described in claim 1,2,7 or 8 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, it is characterized in that: described anti-infectives is selected from a kind of in cefradine, cefalexin, Roxithromycin, azithromycin, amoxicillin, ciprofloxacin, norfloxacin.

11. is according to claim 7 for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation, and it is characterized in that: described natural polymer is selected from a kind of in hyaluronic acid, gelatin, chitosan;

Described solubilizing agent is selected from a kind of in alkylphenol polyoxyethylene, polyoxyethylate amide, Polyethylene Glycol, polyethylene-b-polylactic acid;

Described cosolvent is selected from a kind of in benzoic acid, sodium benzoate, salicylic acid, sodium salicylate, carbamide, nicotinic acid amide, acetamide;

Described amphipathic nature block polymer contains hydrophilic segment and hydrophobic segment simultaneously, hydrophilic segment is selected from a kind of in Polyethylene Glycol, polyoxyethylene, polyvinylpyrrolidone, and hydrophobic segment is selected from a kind of in polylactic acid, poly lactic coglycolic acid, poly-epsilon-caprolactone, poly-β-benzyl Aspartic Acid, poly-benzyl glutamic acid.

12. 1 kinds according to the preparation method for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation described in claim 1～11 any one, it is characterized in that:

(1) polymer dissolution that will carry out electrostatic spinning is in organic solvent and stir, and obtaining volumetric concentration is the polymer electrospun solution of 50～500mg/mL;

(2) polymer electrospun solution step (1) being obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtains polymer nanofibre film substrate;

(3) the biodegradable macromolecule dissolution that will carry out electrostatic spinning is in organic solvent, obtain biodegradable macromolecular solution, then anti-infectives is directly scattered in biodegradable macromolecular solution, stir, obtain the biodegradable polymer electrostatic spinning solution of medicine carrying; The volumetric concentration of described biodegradable macromolecule in electrostatic spinning solution is 50～500mg/mL, and the volumetric concentration of described anti-infectives in electrostatic spinning solution is 1～10mg/mL; Or anti-infectives and solubilizing agent or cosolvent are scattered in biodegradable macromolecular solution, stir, obtain the biodegradable polymer electrostatic spinning solution of medicine carrying; The volumetric concentration of described biodegradable macromolecule in electrostatic spinning solution is 50～500mg/mL, the volumetric concentration of described anti-infectives in electrostatic spinning solution is 1～10mg/mL, and described solubilizing agent or the cosolvent volumetric concentration in the biodegradable polymer electrostatic spinning solution of medicine carrying is 1～10mg/mL;

(4) on the metal dash receiver of the ground connection when polymer nanofibre film substrate directly step (2) being made is placed in and carries out electrostatic spinning, then the biodegradable polymer electrostatic spinning solution of medicine carrying step (3) being obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, and making to carry out the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on polymer nanofibre film substrate; Or

The biodegradable polymer electrostatic spinning solution of medicine carrying that step (3) is obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtains the biodegradable high polymer nanometer fiber functional membrane that load has anti-infectives; Then polymer nanofibre film substrate step (2) being made with carry out after load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be superimposed carrying out heat fusion by heating, or by binding agent, undertaken bondingly, or be connected by suture way;

(5) composite electrostatic spinning nano fibrous membrane step (4) being obtained is placed in vacuum drying oven, thoroughly removes remaining organic solvent, makes for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation;

Or

(a) polymer dissolution that will carry out electrostatic spinning is in organic solvent and stir, and obtaining volumetric concentration is the polymer electrospun solution of 50～500mg/mL;

(b) polymer electrospun solution step (a) being obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtains polymer nanofibre film substrate;

(c) the biodegradable macromolecule dissolution that will carry out electrostatic spinning is in organic solvent and stir, and obtaining volumetric concentration is the biodegradable polymer electrostatic spinning solution of 50～500mg/mL;

(d) anti-infectives that will load is dissolved in separately in solvent and stirs, and obtaining volumetric concentration is the anti-infectives solution of 1～10mg/mL; Or anti-infectives that will load is dissolved in solvent and stirs together with natural polymer, the volumetric concentration that obtains anti-infectives is 1～10mg/mL, the anti-infectives solution that the volumetric concentration of natural polymer is 1～100mg/mL;

(e) on the metal dash receiver of the ground connection when polymer nanofibre film substrate directly step (b) being made is placed in and carries out coaxial electrostatic spinning, then the anti-infectives solution that biodegradable polymer electrostatic spinning solution step (c) being obtained and step (d) obtain is injected into respectively in two liquid storage containers of charging gear of electrostatic spinning apparatus, the liquid storage container that is mounted with anti-infectives solution is connected with the inner tube of a coaxial spinning head by feeder sleeve, the liquid storage container that is mounted with biodegradable polymer electrostatic spinning solution is connected with the outer tube of described coaxial spinning head by feeder sleeve, the pump of opening charging gear carries out coaxial electrostatic spinning, make to carry out that coaxial electrostatic spinning obtains obtains anti-infectives as core, biodegradable macromolecule has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on polymer nanofibre film substrate as the load of the nucleocapsid structure of shell, or

The anti-infectives solution that the biodegradable polymer electrostatic spinning solution that step (c) is obtained and step (d) obtain is injected into respectively in two liquid storage containers of charging gear of electrostatic spinning apparatus, the liquid storage container that is mounted with anti-infectives solution is connected with the inner tube of a coaxial spinning head by feeder sleeve, and the liquid storage container that is mounted with biodegradable polymer electrostatic spinning solution is connected with the outer tube of described coaxial spinning head by feeder sleeve; The pump of opening charging gear carries out coaxial electrostatic spinning, obtains anti-infectives as core, and biodegradable macromolecule has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives as the load of the nucleocapsid structure of shell; Then polymer nanofibre film substrate step (b) being made with carry out anti-infectives that coaxial electrostatic spinning obtains as core, after biodegradable macromolecule has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be superimposed as the load of shell, by heating, carrying out heat merges, or by binding agent, undertaken bondingly, or be connected by suture way;

(f) composite electrostatic spinning nano fibrous membrane step (e) being obtained is placed in vacuum drying oven, thoroughly removes remaining organic solvent, makes for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation;

Biodegradable polymer electrostatic spinning solution during described coaxial electrostatic spinning and the feed volume ratio of anti-infectives solution are 7:1～3:1;

Or

(I) polymer dissolution that will carry out electrostatic spinning is in organic solvent and stir, and obtaining volumetric concentration is the polymer electrospun solution of 50～500mg/mL;

(II) polymer electrospun solution step (I) being obtained is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtains polymer nanofibre film substrate;

(III) the biodegradable macromolecule dissolution that will carry out electrostatic spinning is in organic solvent and stir, and obtaining volumetric concentration is the biodegradable polymer electrostatic spinning solution of 50～500mg/mL;

(IV) anti-infectives is joined in the solution that contains amphipathic nature block polymer reverse micelle obtaining while preparing amphipathic nature block polymer reverse micelle, obtain being embedded with the drug delivery system of the amphipathic nature block polymer reverse micelle of anti-infectives; Wherein, the content of anti-infectives be account for the amphipathic nature block polymer reverse micelle that is embedded with anti-infectives drug delivery system gross weight 5%～50%;

(V) on the metal dash receiver of the ground connection when polymer nanofibre film substrate directly step (II) being made is placed in and carries out electrostatic spinning, the drug delivery system of the amphipathic nature block polymer reverse micelle that is embedded with anti-infectives then step (IV) being obtained is dispersed in the biodegradable polymer electrostatic spinning solution that step (III) obtains, fully stir, obtain electrostatic spinning mixed solution; Wherein, the volumetric concentration of described biodegradable macromolecule in electrostatic spinning mixed solution is 50～500mg/mL, and the volumetric concentration of the described amphipathic nature block polymer reverse micelle that is embedded with anti-infectives in electrostatic spinning mixed solution is 1～50mg/mL; Electrostatic spinning mixed solution is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, making to carry out the load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be directly molded on polymer nanofibre film substrate; Or

The drug delivery system of the amphipathic nature block polymer reverse micelle that is embedded with anti-infectives that step (IV) is obtained is dispersed in the biodegradable polymer electrostatic spinning solution that step (III) obtains, fully stir, obtain electrostatic spinning mixed solution; Wherein, the volumetric concentration of described biodegradable macromolecule in electrostatic spinning mixed solution is 50～500mg/mL, and the volumetric concentration of the described amphipathic nature block polymer reverse micelle that is embedded with anti-infectives in electrostatic spinning mixed solution is 1～50mg/mL; Electrostatic spinning mixed solution is injected in the charging gear of electrostatic spinning apparatus and carries out electrostatic spinning, obtain the biodegradable high polymer nanometer fiber functional membrane that load has anti-infectives; Then polymer nanofibre film substrate step (II) being made with carry out after load that electrostatic spinning obtains has the biodegradable high polymer nanometer fiber functional membrane of anti-infectives to be superimposed carrying out heat fusion by heating, or by binding agent, undertaken bondingly, or be connected by suture way;

(VI) composite electrostatic spinning nano fibrous membrane step (V) being obtained is placed in vacuum drying oven, thoroughly removes remaining organic solvent, makes for anti-infective composite electrostatic spinning nano fibrous membrane hernia patch after performing the operation.

13. preparation methoies according to claim 12, it is characterized in that: step (1), step (3), step (a), step (c), step (I) are selected from acetone, oxolane, chloroform, dichloromethane, chloroform, N with the organic solvent described in step (III), one or more in dinethylformamide, N,N-dimethylacetamide, trifluoroacetic acid;

Solvent described in step (d) is selected from one or more in water, acetone, oxolane, chloroform, dichloromethane, chloroform, DMF, N,N-dimethylacetamide.