CN101332311B - Drug-loaded mesh grid with slow-release function, production method and use thereof - Google Patents
Drug-loaded mesh grid with slow-release function, production method and use thereof Download PDFInfo
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- CN101332311B CN101332311B CN2007101235076A CN200710123507A CN101332311B CN 101332311 B CN101332311 B CN 101332311B CN 2007101235076 A CN2007101235076 A CN 2007101235076A CN 200710123507 A CN200710123507 A CN 200710123507A CN 101332311 B CN101332311 B CN 101332311B
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Abstract
The invention provides a drug-loading weave net which has the drug release function, the manufacturing method and the usage thereof. The drug-loading woven net comprises a weave net, a matrix and the drugs loaded, and can be used as a soft tissue repair material, a cardiac pacemaker or the antibacterial bag of a defibrillator, and so on.
Description
Technical field
The present invention relates to a kind of medicine carrying mesh grid with medicament slow release function, its manufacturing approach and uses thereof.
Background technology
Mesh grid, particularly polypropylene woven net are a kind of medical materials of present extensive use, and especially as patching material, the compatibility of itself and bio-tissue is good, no rejection, and post-operative complication is few, and relapse rate is low, and clinical effectiveness is excellent.But in recent years, doctor and patient find that gradually also there are some problems in the polypropylene woven net in application.For example, behind the implantation polypropylene woven net postoperative infection takes place, or follow pain etc.
Summary of the invention
The present invention accomplishes in view of above-mentioned prior art problems, and its objective is provides:
(1) a kind of medicine carrying mesh grid with medicament slow release function, it comprises mesh grid, substrate and contained medicine.
(2) above-mentioned (1) described medicine carrying mesh grid, wherein said mesh grid is the polypropylene woven net.
(3) the described medicine carrying mesh grid in above-mentioned (1) or (2), wherein said mesh grid are the mesh grids through surface treatment and/or modification.
(4) above-mentioned (3) described medicine carrying mesh grid, wherein said surface treatment or modification are carried out through chemical method and/or plasma method.
(5) any described medicine carrying mesh grid in above-mentioned (1)～(4), wherein contained medicine are easing pain and diminishing inflammation class medicine, anesthesia type medicine or antibiotics.
(6) any described medicine carrying mesh grid in above-mentioned (1)～(5), wherein said medicine is rifampicin, ibuprofen or bupivacaine.
(7) any described medicine carrying mesh grid in above-mentioned (1)～(6), wherein said substrate is Biodegradable polymer or non-biodegradation type polymer.
(8) any described medicine carrying mesh grid in above-mentioned (1)～(7), wherein said substrate are polylactic acid, chitosan or their mixture.
(9) manufacturing approach of any described medicine carrying mesh grid in above-mentioned (1)～(8); This method comprises: substrate and medicine are dissolved in respectively in the solvent, gained solution is mixed after filter membrane is extruded degerming, perhaps directly be dissolved in substrate and medicine in the solvent together; Then gained solution is extruded degerming through filter membrane; The polypropylene woven net is immersed in the solution after the above-mentioned degerming, take out, treat that substrate film forming after drying removes residual solvent.
(10) manufacturing approach of above-mentioned (9) described medicine carrying mesh grid, it further is included in and substrate and medicine is attached to surface treatment and/or modification are carried out in mesh grid before the mesh grid.
(11) manufacturing approach of above-mentioned (10) described medicine carrying mesh grid, wherein said surface treatment or modification are carried out through chemical method and/or plasma method.
(11) manufacturing approach of any described medicine carrying mesh grid in above-mentioned (9)～(11); Wherein said solvent is to be selected from acetone, ethyl acetate, butyl acetate, butanone, Ethyl formate, isobutyl acetate, methyl acetate, propyl acetate, chloroform, dichloromethane, N-Methyl pyrrolidone, 1, one or more materials in 4-dioxane and the dimethyl sulfoxide.
(12) any described medicine carrying mesh grid is used to make the purposes of soft tissue patching material in above-mentioned (1)～(8).
(13) above-mentioned (12) described purposes, wherein said soft tissue patching material are patching materials at the bottom of hernia patching material or the basin.
(14) any described medicine carrying mesh grid is used to make the purposes of heart heartstart or the antibacterial bag of defibrillator in above-mentioned (1)～(8).
Term " mesh grid " used among the application is meant the netted fabric that comprises a large amount of apertures, and wherein braiding comprises that monofilament is knitting, multifilament is knitting, monofilament is woven, multifilament is woven etc.Filament diameter can be 0.1～0.2mm, and thickness can be 0.4～0.8mm, is preferably 0.5～0.7mm.For example, in U.S. Patent No. 5,356,432 discloses several knit mesh, such as polypropylene monofilament knit shape, for example, from CRBard? Inc. Purchased Marlex
; Alternatively, you can use the Prolene
, Dacron
, Teflon
, Merselene
, good release
, and so,
The material that constitutes the mesh grid among the present invention includes but not limited to macromolecular materials such as polyester, politef, polyethylene, polypropylene, wherein preferred present most widely used polypropylene.
In medicine carrying mesh grid of the present invention, substrate can be attached to medicine in the mesh grid, and medicine progressively continues along with the degraded of substrate to discharge or continue to discharge through diffusion.Substrate comprises Biodegradable substrate and non-biodegradation type substrate, and non-biodegradation type substrate (for example vinyl acetate) is the excellent drug carrier, and medicine can progressively disengage with the mode of disperse, but final returning can stay the carrier foreign body.Biodegradable substrate has many advantages: substrate is degraded with stable speed from the periphery to the center in the body, so drug release is stable; Can prevent that medicine is hydrolyzed destruction, keep original activity; The drug release longer duration; Can not stay foreign body in the final body.So matrix optimization Biodegradable substrate of the present invention.
Coating technology capable of using is attached to substrate on the woven mesh materials.
Substrate of the present invention includes but not limited to following material: ethylene-vinyl acetate copolymer (EVA), silicone rubber, polyurethane non-biodegradation type macromolecules such as (PU); Polylactic acid, chitosan, gather Biodegradable macromolecules such as anhydride, polyamino acid, polyphosphazene, collagen, hyaluronic acid, sodium alginate; And other novel macromolecular material, for example novel tree-like (dendrimer), hyperbranched (hyperbranched) macromolecules such as polyamide-amide (PAMAM), Polyol.These materials can use separately, perhaps also can as required combination more than 2 kinds be used.
In the cited above-mentioned substance of substrate of the present invention, polylactic acid (PLA) is the macromolecular material of present extensive use, has good biocompatibility, is ratified by FDA.Chitosan (chitosan) can suppress antibacterial, fungus growth, is constrained to fibrocellular activity.Because the existence of polar group, chitosan has very high affinity and retentiveness to water, can be dissolved in the weak acid, is filmogen very easily.Chitosan has excellent biological compatibility and biological degradability, and catabolite generally to the human non-toxic side effect, is not put aside in vivo, non-immunogenicity.
The ingredient that is used for medicine carrying mesh grid of the present invention can be a kind of medicine, also can be the mixture of two or more medicines.This medicine includes but not limited to: easing pain and diminishing inflammation class medicine, anesthesia type medicine and antibiotics.Wherein for example ibuprofen (ibuprofen) can be enumerated in the analgesic drug, and an anesthesia type medicine can be enumerated for example bupivacaine (bupivacaine), and antibiotics can be enumerated for example rifampicin (rifampicin).
The medicine carrying mesh grid that the present invention has slow-release function can be implanted to the position that needs through modes such as surgical operation or scopes, thus in this position with certain release time (for example from hour by several days) and its contained medicine of burst size release.
It is different because of the kind of medicine that the present invention has the contained medication amount of the medicine carrying mesh grid of slow-release function, and those skilled in the art can rationally confirm according to the purposes of this medicine carrying mesh grid and the known conventional consumption of contained medicine etc.For example, the drug loading of rifampicin, ibuprofen and bupivacaine generally is preferably the mesh grid of 1～20mg/ square centimeter.
In addition, do not limit, be preferably the mesh grid of 0.1～2g/ square centimeter the substrates quantity in the medicine carrying mesh grid of the present invention is special.
Medicine carrying mesh grid of the present invention can be according to following method manufacturing: be dissolved in substrate and medicine in the solvent respectively; Gained solution is mixed after filter membrane is extruded degerming, perhaps directly substrate and medicine are dissolved in the solvent together, then gained solution is extruded degerming through filter membrane; Mesh grid is immersed in the solution after the above-mentioned degerming; Take out, take out the dry residual solvent of removing after the film forming, packing.
In preferred version of the present invention; For substrate is combined with mesh grid more securely; In above-mentioned manufacturing approach, further be included in and substrate and medicine be attached to through chemistry and/or plasma method etc. surface treatment and/or modification are carried out in mesh grid in advance before the mesh grid.
In another preferred version of the present invention, the time that above-mentioned mesh grid is immersed in the solution is about 1～15 minute.
To being used to make the not special restriction of solvent that the present invention has the medicine carrying mesh grid of slow-release function; Can enumerate acetone, ethyl acetate, butyl acetate, butanone, Ethyl formate, isobutyl acetate, methyl acetate, propyl acetate, chloroform, dichloromethane, N-Methyl pyrrolidone, 1,4-dioxane and dimethyl sulfoxide etc.These solvents can use separately, perhaps as required two or more combinations are used.
The medicine carrying mesh grid that the present invention has slow-release function can continue to discharge easing pain and diminishing inflammation class medicine, anesthesia type medicine, antibiotics etc. at affected part, thereby can alleviate postoperative pain, or reduces infection risk.
Description of drawings
Fig. 1 is the rifampicin time-accumulative total release rate curve of the medicine carrying polypropylene woven net of the embodiment of the invention 1.
Fig. 2 is the ibuprofen time-accumulative total release rate curve of the medicine carrying polypropylene woven net of the embodiment of the invention 3.
Fig. 3 is the bupivacaine time-accumulative total release rate curve of the medicine carrying polypropylene woven net of the embodiment of the invention 5.
The specific embodiment
Specify the present invention through embodiment below, but scope of the present invention is not limited to these embodiment.Under situation without departing from the spirit and scope of the present invention, those of ordinary skills can make various changes and improvement to the present invention in form and details, and these improvement and change all are considered to fall into scope of the present invention.
With 1g polylactic acid (Mw=100; 000), the 10mg rifampicin is dissolved in the 50ml ethyl acetate, and gained solution is extruded degerming through 0.2 μ m filter membrane, will wash dried 1 * 1cm polypropylene woven net and immerse taking-up after about 5 minutes in the above-mentioned solution; Treat that ethyl acetate volatilization film forming postposition goes into (40 ℃ in vacuum drying oven; 76mmHg 48h) removes residual ethyl acetate, and kept dry is subsequent use.
With 1g polylactic acid (Mw=100; 000), the 10mg rifampicin is dissolved in the 50ml ethyl acetate; Gained solution is extruded degerming through 0.2 μ m filter membrane; To wash dried 1 * 1cm polypropylene woven net and insert in the low-temperature plasma device, under the condition of hydrogen flow rate 1L/min, nitrogen flow rate 0.5L/min, discharge power 100W, handle 2min.The polypropylene woven net of handling immersed in the above-mentioned solution after about 5 minutes takes out, treat ethyl acetate volatilization film forming postposition go into vacuum drying oven (40 ℃, 76mmHg 48h) removes residual ethyl acetate, kept dry is subsequent use.
With 1g polylactic acid (Mw=200,000), 0.2g chitosan (deacetylation 80%, Mw=150; 000), the 10mg ibuprofen is dissolved in the 50ml acetone, and gained solution is extruded degerming through 0.2 μ m filter membrane, will wash dried 1 * 1cm polypropylene woven net and immerse taking-up after about 5 minutes in the above-mentioned solution; Treat that acetone volatilization film forming postposition goes into (40 ℃ in vacuum drying oven; 76mmHg 48h) removes residual acetone, and kept dry is subsequent use.
With 1g polylactic acid (Mw=50; 000), the 10mg ibuprofen is dissolved in the 50ml chloroform; Gained solution is extruded degerming through 0.2 μ m filter membrane; To wash dried 1 * 1cm polypropylene woven net and insert in the low-temperature plasma device, under the condition of hydrogen flow rate 1L/min, nitrogen flow rate 0.5L/min, discharge power 100W, handle 2min.The polypropylene woven net of handling immersed in the above-mentioned solution after about 5 minutes takes out, treat chloroform volatilization film forming postposition go into vacuum drying oven (40 ℃, 76mmHg 48h) removes residual chloroform, kept dry is subsequent use.
With 1g chitosan (deacetylation 50%; Mw=100,000), the 10mg bupivacaine is dissolved in the acetum of 50ml 2%, and gained solution is extruded degerming through 0.2 μ m filter membrane; To wash dried 1 * 1cm polypropylene woven net and immerse taking-up after about 5 minutes in the above-mentioned solution; Insert after the film forming vacuum drying oven (50 ℃, 76mmHg, 48h) dry back is preserved subsequent use.
With 1g poly-D-lysine (Mw=200; 000), the 5mg bupivacaine is dissolved in the 50ml deionized water; Gained solution is extruded degerming through 0.2 μ m filter membrane; To wash the polypropylene woven net of dried 1 * 1cm and insert in the low-temperature plasma device, under the condition of hydrogen flow rate 1L/min, nitrogen flow rate 0.5L/min, discharge power 100W, handle 2min.The polypropylene woven net of handling immersed in the above-mentioned solution after about 5 minutes takes out, insert after the film forming vacuum drying oven (50 ℃, 76mmHg, 48h), kept dry is subsequent use.
Replace the polypropylene woven net with the woven polyethylene net, all the other are according to obtaining medicine carrying woven polyethylene net with embodiment 1 same method.
Embodiment 8
Replace the polypropylene woven net with the woven polyethylene net, all the other are according to obtaining medicine carrying woven polyethylene net with embodiment 2 same methods.
Replace the polypropylene woven net with the PETG mesh grid, all the other are according to obtaining the mesh grid of medicine carrying PETG with embodiment 1 same method.
Replace the polypropylene woven net with the PETG mesh grid, all the other are according to obtaining the mesh grid of medicine carrying PETG with embodiment 2 same methods.
Embodiment 11
The polypropylene woven net of making in the foregoing description 1 is inserted in the bottle of the PBS (PBS) that 10ml 0.1mol/L (pH=7.4) is housed, and 37 ℃ are soaked 24h; Take out mesh grid and change to fresh PBS solution for continuous and soak, every 24h changes liquid once.Rifampicin concentration in the leachate is recorded by HPLC (HPLC), calculates the accumulative total release rate of rifampicin according to the standard curve method.
Accumulative total release rate (%)=accumulative total burst size (mg)/contained medicine total amount (mg) * 100%
Chromatographic condition: C
18Post (4 μ m, 150mm * 3.9mm), mobile phase is methanol/sodium acetate (0.02mol/L) mixed solution of 3: 2, flow velocity 1.0ml/min, 20 ℃ of column temperatures, sample size 10 μ l detect wavelength 334nm.
The result: as shown in Figure 1, extracorporeal releasing experiment shows that the 1st day rifampicin release rate is 31.4%, and rate of release descends gradually afterwards, and the rifampicin accumulative total release rate of drug release after 7 days is 84.2%.
In addition, respectively the medicine carrying polypropylene woven net of embodiment 3 and 5 is measured according to method same as described above, the result respectively as shown in Figures 2 and 3.
Claims (1)
1. a manufacturing has the method for the medicine carrying mesh grid of medicament slow release function; This method comprises: substrate and medicine are dissolved in respectively in the solvent, gained solution is mixed after filter membrane is extruded degerming, perhaps directly be dissolved in substrate and medicine in the solvent together; Then gained solution is extruded degerming through filter membrane; Mesh grid was immersed in the solution after the above-mentioned degerming 1-15 minute, take out, treat that substrate film forming after drying removes residual solvent;
Substrates quantity in the medicine carrying mesh grid is the mesh grid of 0.1g-2g/ square centimeter;
Drug loading is the mesh grid of 1-20mg/ square centimeter;
In that being attached to, substrate and medicine through chemical method and/or plasma method surface treatment and/or modification are carried out in mesh grid before the mesh grid;
Contained medicine is easing pain and diminishing inflammation class medicine, anesthesia type medicine or antibiotics;
Said substrate is Biodegradable polymer or non-biodegradation type polymer;
Polypropylene woven net or woven polyethylene net are used in mesh grid;
This medicine carrying mesh grid is used to make antibacterial bag of heart heartstart or the antibacterial bag of defibrillator.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101235076A CN101332311B (en) | 2007-06-29 | 2007-06-29 | Drug-loaded mesh grid with slow-release function, production method and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101235076A CN101332311B (en) | 2007-06-29 | 2007-06-29 | Drug-loaded mesh grid with slow-release function, production method and use thereof |
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| Publication Number | Publication Date |
|---|---|
| CN101332311A CN101332311A (en) | 2008-12-31 |
| CN101332311B true CN101332311B (en) | 2012-01-11 |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102217981B (en) * | 2011-05-16 | 2013-06-12 | 北京天助畅运医疗技术股份有限公司 | Multi-layer hernia repairing patch and preparation method thereof |
| CN102302800B (en) * | 2011-09-14 | 2013-12-11 | 上海市第六人民医院 | Chitosan biofilm polypropylene mesh and preparation method thereof |
| CN103028144B (en) * | 2011-09-30 | 2014-10-29 | 王明刚 | Tension-free hernia patch and preparation method thereof |
| CN103463679B (en) * | 2013-09-04 | 2015-11-18 | 江苏知原药业有限公司 | A kind of hernia mesh plug prepared with modified polypropylene fiber filaments screen cloth |
| CN105709280B (en) * | 2014-12-18 | 2019-01-18 | 上海微创医疗器械（集团）有限公司 | Anti-infective cladding bag of one kind and preparation method thereof |
| WO2016095824A1 (en) * | 2014-12-18 | 2016-06-23 | 上海微创医疗器械（集团）有限公司 | Anti-infective dressing bag and fabricating method therefor |
| EP3310435A1 (en) | 2015-06-18 | 2018-04-25 | Cardiac Pacemakers, Inc. | Polymer cover for an implantable medical device, the cover comprising a bioresorbable polymer and an antimicrobial agent, and a method for its production |
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|---|---|---|---|---|
| CN86104141A (en) * | 1986-12-25 | 1988-07-13 | 珊瑚化工厂 | The preparation method of polyacrylic esters containing medicine of slow release formulation |
| US5356432A (en) * | 1993-02-05 | 1994-10-18 | C. R. Bard, Inc. | Implantable mesh prosthesis and method for repairing muscle or tissue wall defects |
| CN1317297A (en) * | 2000-04-11 | 2001-10-17 | 张保军 | Absorbable artificial dura meter of brain and its preparing process |
| CN1529653A (en) * | 2001-05-16 | 2004-09-15 | �й���ѧԺ���ݻ�ѧ�о��� | Biodegradable and/or biological absorbing fiber product and its use in medical application |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN86104141A (en) * | 1986-12-25 | 1988-07-13 | 珊瑚化工厂 | The preparation method of polyacrylic esters containing medicine of slow release formulation |
| US5356432A (en) * | 1993-02-05 | 1994-10-18 | C. R. Bard, Inc. | Implantable mesh prosthesis and method for repairing muscle or tissue wall defects |
| US5356432B1 (en) * | 1993-02-05 | 1997-02-04 | Bard Inc C R | Implantable mesh prosthesis and method for repairing muscle or tissue wall defects |
| CN1317297A (en) * | 2000-04-11 | 2001-10-17 | 张保军 | Absorbable artificial dura meter of brain and its preparing process |
| CN1529653A (en) * | 2001-05-16 | 2004-09-15 | �й���ѧԺ���ݻ�ѧ�о��� | Biodegradable and/or biological absorbing fiber product and its use in medical application |
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